<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03036800</url>
  </required_header>
  <id_info>
    <org_study_id>0626</org_study_id>
    <nct_id>NCT03036800</nct_id>
  </id_info>
  <brief_title>Saxenda in Obesity Services (STRIVE Study)</brief_title>
  <acronym>STRIVE</acronym>
  <official_title>EFFECTIVENESS AND COST OF INTEGRATING A PROTOCOL WITH USE OF LIRAGLUTIDE 3.0 MG INTO AN OBESITY SERVICE: (STRIVE Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Leicester</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novo Nordisk A/S</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Leicester</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      A two year, parallel, two group, open-label, real-world randomised controlled trial (RCT)&#xD;
      design for subjects with severe and complex obesity who are referred to a Tier 3 or&#xD;
      equivalent specialist weight management/obesity service. Participants will be randomised to&#xD;
      receive 1) standard care (obesity-specialist care), or 2) targeted prescribing pathway&#xD;
      (obesity-specialist care plus targeted use of Liraglutide 3.0mg [LIRA 3mg] with pre-specified&#xD;
      stopping rules for the medication). The aim of the study is to compare the effectiveness,&#xD;
      budget impact, and cost-effectiveness between the two groups in a real-world setting among&#xD;
      otherwise largely unselected patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Summary of Trial Design A two year, parallel, two group, open-label, real-world, RCT design&#xD;
      for patients with severe and complex obesity who are referred to a Tier 3 obesity service&#xD;
      (including patients who are referred to a Tier 3 service as part of the bariatric surgery&#xD;
      pathway). The total duration of participation will be 104 weeks (+/-2 weeks).&#xD;
&#xD;
      The first 52 weeks of the study (after randomisation) will determine whether using the&#xD;
      targeted prescribing pathway in a Tier 3 setting will result in more participants attaining&#xD;
      ≥15% weight loss compared with standard care. The second 52 weeks of the study will assess&#xD;
      whether patients who lose ≥15% of their baseline weight by the first 52 weeks are more likely&#xD;
      to maintain ≥15% weight loss for another 52 weeks in the targeted prescribing pathway&#xD;
      compared with standard care. Further, budget impact, cost-effectiveness, improvement in&#xD;
      obesity-related co-morbidities, complementary aspects of safety, effectiveness, adherence,&#xD;
      and treatment satisfaction of both treatment groups will be assessed and compared.&#xD;
&#xD;
      Participants will be randomised in a 2:1 fashion to either the intervention (targeted&#xD;
      prescribing pathway + standard care) or control (standard care) group (2 intervention: 1&#xD;
      control). The control group will receive standard care in a specialist obesity service (Tier&#xD;
      3 or equivalent), according to the best practice in each site and can include total or&#xD;
      partial meal replacement strategies. The intervention group will receive the same standard&#xD;
      care as the control group (i.e. according to the best practice in each site) plus all&#xD;
      participants will initially receive LIRA with pre-specified stopping rules. The targeted&#xD;
      prescribing pathway: participants who do not meet the definition of a 'early and good&#xD;
      responder' (defined as achieving ≥5% weight loss at 16 weeks, ≥10% weight loss at 32 weeks&#xD;
      and ≥15% weight loss at 52 weeks) will have their LIRA 3mg treatment stopped. It is important&#xD;
      to note that all participants will be analysed in the group to which they are randomised; in&#xD;
      particular, participants in the intervention group who stop receiving LIRA 3mg will remain in&#xD;
      the intervention group and will continue to receive standard care for the remainder of the&#xD;
      study as per the targeted prescribing pathway (albeit, the part of the pathway where LIRA 3mg&#xD;
      is not prescribed; see Figure 1).&#xD;
&#xD;
      The study is intentionally designed to reflect a pragmatic &quot;real-world&quot; scenario and each&#xD;
      Tier 3 provider may require a different number of visits for their programme. However, study&#xD;
      appointments for data collection, titration reviews, application of the stopping rules of&#xD;
      LIRA 3mg, and dispensing will be standardised for all of the five sites.&#xD;
&#xD;
      Intervention (Targeted Prescribing Pathway)&#xD;
&#xD;
      The NHS Weight Management pathway is divided into four distinct tiers:&#xD;
&#xD;
      Tier 1: health promotion Tier 2: lifestyle interventions Tier 3: specialist multidisciplinary&#xD;
      weight management services Tier 4: bariatric surgery&#xD;
&#xD;
      Across the UK, each region has a specialist Tier 3 obesity and/or weight management service&#xD;
      or equivalent, usually referred to as Tier 3. This includes a clinician led multidisciplinary&#xD;
      team approach, potentially including a specialist physician, nurse, dietician, psychologist,&#xD;
      physiotherapist, etc. From this point forwards, Tier 3 specialist weight management and/or&#xD;
      equivalent services will be referred to as 'Tier 3' throughout the remainder of this&#xD;
      protocol.&#xD;
&#xD;
      Participants in the intervention group will receive the same standard care as those in the&#xD;
      control group, i.e. the best medical practice delivered by the Tier 3 service at each site.&#xD;
      Additionally, at baseline, LIRA 3mg will be prescribed to all of the participants in the&#xD;
      intervention group at a starting dose of 0.6mg daily. Dose escalation of Liraglutide will&#xD;
      occur according to a pre-specified titration protocol, from 0.6mg to a maximum of 3.0mg&#xD;
      daily. Liraglutide dose will be initiated at 0.6mg and then increased to 1.2mg in Week 2,&#xD;
      1.8mg in Week 3, 2.4mg in Week 4, and 3.0mg in Week 5. Participants in the intervention group&#xD;
      will be aware that the LIRA 3mg treatment may be stopped at various time points throughout&#xD;
      the duration of the study and that continued use of LIRA 3mg is based upon their response to&#xD;
      the treatment in terms of them achieving pre-defined weight loss targets at 16, 32 and 52&#xD;
      weeks.. Specifically, participants in the intervention group will continue to be prescribed&#xD;
      LIRA 3mg for the 104 week duration of the study, unless one of the following stopping rules&#xD;
      applies:&#xD;
&#xD;
        1. st stopping rule: After 16 weeks (± 14 days) on the medication, only those participants&#xD;
           who have lost ≥5% of their baseline weight will be offered further treatment with LIRA&#xD;
           3mg for another 16 weeks. Participants who have not met this weight loss target will&#xD;
           have their LIRA 3mg treatment stopped but will still continue in the targeted&#xD;
           prescribing pathway but will receive standard care only during the remainder of the&#xD;
           study.&#xD;
&#xD;
        2. nd stopping rule: After 32 weeks (± 14 days) on the medication, only those participants&#xD;
           who have lost ≥10% of their baseline weight and are still on treatment with LIRA 3mg&#xD;
           will be offered another 20 weeks on LIRA 3mg. Participants who have not met this weight&#xD;
           loss target will have their LIRA 3mg treatment stopped but will still continue in the&#xD;
           targeted prescribing pathway but will receive standard care only during the remainder of&#xD;
           the study.&#xD;
&#xD;
        3. rd stopping rule: After the first year of treatment (week 52; ± 14 days), only those&#xD;
           participants who have lost ≥15% of their baseline weight and are still on treatment with&#xD;
           LIRA 3mg will be offered another 52 weeks on LIRA 3mg. Participants who have not met&#xD;
           this weight loss target will have their LIRA 3mg treatment stopped but will still&#xD;
           continue in the targeted prescribing pathway but will receive standard care only during&#xD;
           the remainder of the study.&#xD;
&#xD;
      Participants who fail to reach the pre-defined weight-loss targets to continue LIRA 3mg&#xD;
      treatment, or who choose to stop receiving LIRA 3mg, will continue to be offered the standard&#xD;
      care provided by the Tier 3 service. These participants will still attend the Clinical Review&#xD;
      Visits but not the additional visits for participants who are still on LIRA 3mg (e.g. Weeks&#xD;
      65 &amp; 91) because these visits will not be relevant to them; visits at Weeks 65 and 91 are&#xD;
      intended to provide a new prescription of LIRA 3mg and to discuss adherence and any side&#xD;
      effects;; see Appendices 2 &amp; 3).&#xD;
&#xD;
      Participants will remain routinely in the Tier 3 service in-line with NICE guidance&#xD;
      throughout the duration of the research study. Participants may be offered treatment options&#xD;
      within the duration of the study, including bariatric surgery, as per NICE guidance and&#xD;
      according to the decision of the local Tier 3 Multidisciplinary Team. Participants who have&#xD;
      undergone bariatric surgery after randomisation will only be included in the intention to&#xD;
      treat (ITT) analysis. This decision was made because the proportion of participants&#xD;
      undergoing bariatric surgery is likely to be unbalanced between the treatment groups (i.e.&#xD;
      more participants in the control group are expected to have bariatric surgery than in the&#xD;
      targeted prescribing pathway treatment group), and thus weight loss in these individuals&#xD;
      could unduly influence the study results. Participants who have been prescribed and start&#xD;
      anti-obesity medication (such as Orlistat) will be ineligible for LIRA 3mg treatment.&#xD;
&#xD;
      Control (Standard Care) Participants in the control group will follow the best medical care&#xD;
      provided by the Tier 3 service at the relevant site. This typically involves dietary advice&#xD;
      to reduce energy intake (and may include a period of partial or total meal replacement),&#xD;
      accompanied - if available - by a physical activity programme, both supported by behavioural&#xD;
      change techniques with regular professional contacts. The nature of the standard care will&#xD;
      vary between the different Tier 3 services at each site, as this is a pragmatic 'real-world'&#xD;
      study. Clinician input will include the medical assessment of participants for severe and&#xD;
      complicated obesity and the prescription of anti-obesity drugs (such as Orlistat) as per&#xD;
      local Tier 3 service policy. As with the LIRA 3mg group those patients taking&#xD;
      antihypertensive or antidepressant medication will be assessed and it will be at the&#xD;
      clinician's discretion as to whether these medications are changed. Participants will remain&#xD;
      routinely in the Tier 3 service in-line with NICE guidance throughout the duration of the&#xD;
      research study. Participants may be offered treatment options within the duration of the&#xD;
      study, including bariatric surgery, as per NICE guidance and according to the decision of the&#xD;
      local Tier 3 Multidisciplinary Team.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">November 28, 2017</start_date>
  <completion_date type="Anticipated">June 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2022</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Weight loss of ≥15% at 52 weeks</measure>
    <time_frame>52 weeks</time_frame>
    <description>The primary outcome of the study will be the proportion of participants with severe and complicated obesity achieving weight loss of ≥15% at 52 weeks with the use of a targeted prescribing pathway (i.e. use of LIRA 3mg according to a pre-specified protocol in combination with standard care provided in Tier 3 services) versus standard care alone in a Tier 3 service.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Budget impact of a Tier 3 weight management service</measure>
    <time_frame>52 &amp; 104 weeks</time_frame>
    <description>Cost of the proposed LIRA 3mg (as per protocol - e.g. actual dose taken = number of days taking study drug x daily cost of drug, or cost of total amount of study drug used)&#xD;
Cost of visits to clinician for assessment and medication prescription during Specialist Weight Management Service programme&#xD;
Cost of visits to dietician during Specialist Weight Management Service programme&#xD;
Cost of visits to psychologist during Specialist Weight Management Service programme&#xD;
Cost of physical activity physiologist/physiotherapist during Specialist Weight Management Service programme (if applicable)&#xD;
Cost of Multidisciplinary Team (MDT) discussion in Specialist Weight Management Service&#xD;
Cost of blood tests in Specialist Weight Management Service&#xD;
Cost of consumables and goods&#xD;
Cost of referral into Tier 4</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Estimated long-term cost-effectiveness</measure>
    <time_frame>104 weeks</time_frame>
    <description>Length of treatment with LIRA 3mg&#xD;
Daily dose of LIRA 3mg (based on actual doses taken)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improving obesity-related comorbidities</measure>
    <time_frame>52 &amp; 104 weeks</time_frame>
    <description>This will be assessed by the Kings College Obesity Staging (KCOS) score. The score is 0-3.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maintenance of ≥15% weight loss until 104 weeks (an additional 52 weeks)</measure>
    <time_frame>104 weeks</time_frame>
    <description>Proportion of participants maintaining weight loss of ≥15% among those who lost ≥15% at 52 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient adherence to treatment</measure>
    <time_frame>16, 32, 52 and 104 weeks</time_frame>
    <description>Study drug reconciliation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Referral rates to other obesity interventions</measure>
    <time_frame>52 and 104 weeks</time_frame>
    <description>Number of participants referred to Tier 4 for bariatric surgery over the 104 weeks study period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety related outcomes</measure>
    <time_frame>52 and 104 weeks</time_frame>
    <description>AE reporting</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction</measure>
    <time_frame>52 and 104 weeks</time_frame>
    <description>Treatment Satisfaction Questionnaire for Medication (TSQM)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient quality of life</measure>
    <time_frame>52 and 104 weeks</time_frame>
    <description>EuroQol five dimension scale (EQ5D) the minimum value is 0 and maximum is 100, low scores are a worse outcome and high scores are a better outcome.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Weight (kg)</measure>
    <time_frame>16, 32, 52 and 104 weeks</time_frame>
    <description>Absolute change in weight from baseline Anthropometric measures: (Kg)</description>
  </other_outcome>
  <other_outcome>
    <measure>Relative change in weight from baseline</measure>
    <time_frame>16, 32, 52 and 104 weeks</time_frame>
    <description>(% change in weight)</description>
  </other_outcome>
  <other_outcome>
    <measure>Physical Activity</measure>
    <time_frame>52 and 104 weeks</time_frame>
    <description>International physical activity questionnaire (IPAQ- Long Form) there is not a scale, this is based on hours and minutes of physical activity. A higher number is a better outcome and a lower number is a worse outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in concomitant medications</measure>
    <time_frame>Screening - 104 weeks</time_frame>
    <description>Concomitant medication reporting</description>
  </other_outcome>
  <other_outcome>
    <measure>Medical History (including surgical history)</measure>
    <time_frame>52 and 104 weeks</time_frame>
    <description>Patient notes</description>
  </other_outcome>
  <other_outcome>
    <measure>HSRUQ (Health service and resource uses questionnaire)</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>Questionnaire</description>
  </other_outcome>
  <other_outcome>
    <measure>Length of treatment with LIRA 3mg</measure>
    <time_frame>52 and 104 weeks</time_frame>
    <description>Days of treatment with LIRA 3mg</description>
  </other_outcome>
  <other_outcome>
    <measure>Daily dose of LIRA 3mg (based on actual doses taken)</measure>
    <time_frame>52 and 104 weeks</time_frame>
    <description>Mg of liraglutide actually taken</description>
  </other_outcome>
  <other_outcome>
    <measure>HbA1C</measure>
    <time_frame>Screening, 32, 52 and 104 weeks</time_frame>
    <description>Biochemistry: IFCC (mmol/mol)</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of participants with normoglycaemia (defined as HbA1C &lt;42.0 mmol/mol without glucose lowering medications)</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>% percentage of the population in each group having normoglycaemia</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of participants with prediabetes (defined as HbA1C 42.0-47.9 mmol/mol without glucose lowering medications)</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>% percentage of the population in each group having prediabetes</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of participants with diabetes (defined as HbA1C ≥48 mmol/mol or on glucose lowering medications)</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>% percentage of the population in each group having type 2 diabetes</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of medications for management of type 2 diabetes</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>Number</description>
  </other_outcome>
  <other_outcome>
    <measure>Dose of medications for management of type 2 diabetes</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>Medications for type 2 diabetes dose</description>
  </other_outcome>
  <other_outcome>
    <measure>Class of medications for type 2 diabetes</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>Medication class for type 2 diabetes</description>
  </other_outcome>
  <other_outcome>
    <measure>Monitoring of Albumin- Creatinine Ratio (ACR) for patients with prediabetes, diabetes and hypertension.</measure>
    <time_frame>Screening, 32, 52 and 104 weeks</time_frame>
    <description>(mg/mmol)</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood pressure</measure>
    <time_frame>Screening - 104 weeks</time_frame>
    <description>(mmHg)</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of participants with hypertension (defined as patients on antihypertensive medications or systolic blood pressure&gt;140mmHg)</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>% percentage of the population in each group having hypertension</description>
  </other_outcome>
  <other_outcome>
    <measure>Dose of antihypertensive medication</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>Dose of medications for treatment of hypertension</description>
  </other_outcome>
  <other_outcome>
    <measure>Class of antihypertensive medications</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>Medication class for treatment of hypertension</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of anti-hypertensive medication</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>Number</description>
  </other_outcome>
  <other_outcome>
    <measure>Epworth score</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>Questionnaire</description>
  </other_outcome>
  <other_outcome>
    <measure>Stop Bang questionnaire</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>Questionnaire</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of participants on CPAP</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>% percentage of the population in each group on CPAP</description>
  </other_outcome>
  <other_outcome>
    <measure>CPAP pressures for patients on variable pressures CPAP</measure>
    <time_frame>screening, 52 and 104 weeks</time_frame>
    <description>Centimeters of water pressure (cm H20)</description>
  </other_outcome>
  <other_outcome>
    <measure>Apnoea Hypopnea Index (AHI) for participants with sleep apnoea who cannot tolerate CPAP or for participants on fixed pressures CPAP</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>Apnoea Hypopnea Index</description>
  </other_outcome>
  <other_outcome>
    <measure>Oxygen desaturation index for participants with sleep apnoea who cannot tolerate CPAP or for participants on fixed pressures CPAP</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>Oxygen desaturation Index</description>
  </other_outcome>
  <other_outcome>
    <measure>Lipids</measure>
    <time_frame>Screening, 32, 52 and 104 weeks</time_frame>
    <description>Biochemistry: Cholesterol (mmol/l), triglycerides (mmol/l), HDL cholesterol (mmol/l), LDL cholesterol (mmol/l), HDL ratio</description>
  </other_outcome>
  <other_outcome>
    <measure>Dose of medication for dyslipidaemia</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>Dose of medications for treatment of dyslipidaemia</description>
  </other_outcome>
  <other_outcome>
    <measure>Class of medications for dyslipidaemia</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>Medication class for treatment of dyslipidaemia</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of medications for dyslipidaemia</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>Number</description>
  </other_outcome>
  <other_outcome>
    <measure>King's College Obesity Staging System assessment</measure>
    <time_frame>Screening, 52 and 104 weeks</time_frame>
    <description>Scoring System</description>
  </other_outcome>
  <other_outcome>
    <measure>The number of participants who did or did not attend at least 70% of the scheduled appointments with the Specialist Weight Management Service (completers)</measure>
    <time_frame>52 and 104 weeks</time_frame>
    <description>Number</description>
  </other_outcome>
  <other_outcome>
    <measure>The number of participants who had to stop treatment with LIRA 3mg because of adverse effects (targeted prescribing pathway only)</measure>
    <time_frame>52 and 104 weeks</time_frame>
    <description>Number</description>
  </other_outcome>
  <other_outcome>
    <measure>The number of participants who stopped LIRA 3mg at 16 weeks after randomization</measure>
    <time_frame>16 weeks</time_frame>
    <description>Number</description>
  </other_outcome>
  <other_outcome>
    <measure>The number of participants who stopped LIRA 3mg at 32 weeks after randomization</measure>
    <time_frame>32 weeks</time_frame>
    <description>Number</description>
  </other_outcome>
  <other_outcome>
    <measure>The number of participants who stopped LIRA 3mg at 52 weeks after randomization</measure>
    <time_frame>52 weeks</time_frame>
    <description>Number</description>
  </other_outcome>
  <other_outcome>
    <measure>The number of participants who completed 52 weeks of the Specialist Weight Management Service programme despite stopping LIRA 3mg at 16 weeks</measure>
    <time_frame>52 weeks</time_frame>
    <description>% percentage</description>
  </other_outcome>
  <other_outcome>
    <measure>The number of participants who completed 52 weeks of the Specialist Weight Management Service programme despite stopping LIRA 3mg at 32 weeks</measure>
    <time_frame>52 weeks</time_frame>
    <description>% percentage</description>
  </other_outcome>
  <other_outcome>
    <measure>The adherence of participants with LIRA 3mg (monitored through return of used pens and questionnaires) - Targeted prescribing pathway only</measure>
    <time_frame>16, 32, 52 and 104 weeks</time_frame>
    <description>% percentage</description>
  </other_outcome>
  <other_outcome>
    <measure>The number of participants started on anti-obesity drugs</measure>
    <time_frame>16, 32, 52 and 104 weeks</time_frame>
    <description>Number</description>
  </other_outcome>
  <other_outcome>
    <measure>The adherence of participants with other anti-obesity medications</measure>
    <time_frame>16, 32, 52 and 104 weeks</time_frame>
    <description>% percentage</description>
  </other_outcome>
  <other_outcome>
    <measure>Gastrointestinal symptoms</measure>
    <time_frame>Baseline, 52 and 104 weeks</time_frame>
    <description>Total number of gastrointestinal symptoms in each group</description>
  </other_outcome>
  <other_outcome>
    <measure>Overall hypoglycaemia rate</measure>
    <time_frame>Baseline, 52 and 104 weeks</time_frame>
    <description>% of patients who experience a hypoglycaemic event in each group</description>
  </other_outcome>
  <other_outcome>
    <measure>Overall AE/SAE rate</measure>
    <time_frame>Baseline, 52 and 104 weeks</time_frame>
    <description>Total number of AE/SAE in each group</description>
  </other_outcome>
  <other_outcome>
    <measure>Rates of severe hypoglycaemia</measure>
    <time_frame>Baseline, 52 and 104 weeks</time_frame>
    <description>% of patients who experience severe hypoglycaemia in each group</description>
  </other_outcome>
  <other_outcome>
    <measure>Heart rate</measure>
    <time_frame>Baseline - 104 weeks</time_frame>
    <description>Pulse/min</description>
  </other_outcome>
  <other_outcome>
    <measure>Impact of Weight on Quality of Life-Lite (IWQOL-Lite)</measure>
    <time_frame>Baseline, 52 and 104 weeks</time_frame>
    <description>The minimum value is 1 and maximum value is 5. A higher number is a worse outcome and a lower number is a better outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Patient Health Questionnaire-9 (PHQ9)</measure>
    <time_frame>Baseline, 52 and 104 weeks</time_frame>
    <description>The minimum value is 0 and maximum value is 3. A higher number is a worse outcome and a lower number is a better outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of participants reaching weight loss of ≥5%, ≥10% and ≥15%</measure>
    <time_frame>16, 32, 52 (except of ≥15% weight loss which is primary outcome) and 104 weeks</time_frame>
    <description>(% percentage)</description>
  </other_outcome>
  <other_outcome>
    <measure>BMI and change in BMI from baseline</measure>
    <time_frame>16, 32, 52 and 104 weeks</time_frame>
    <description>(kg/m2)</description>
  </other_outcome>
  <other_outcome>
    <measure>Waist circumference</measure>
    <time_frame>52 and 104 weeks</time_frame>
    <description>(cm)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">392</enrollment>
  <condition>Obesity</condition>
  <condition>Weight Loss</condition>
  <condition>Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Targeted Prescribing Pathway (LIRA 3mg + Standard Care)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Standard care plus targeted use of the intervention Liraglutide (LIRA) 3mg when pre-specified stopping rules for the medication apply</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard Care</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>standard Tier 3 obesity specialist service care</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saxenda</intervention_name>
    <description>standard care plus targeted use of Liraglutide (LIRA) 3mg when pre-specified stopping rules for the medication apply. Liraglutide (Saxenda) 6 mg/mL solution for injection in pre-filled pen, administered by subcutaneous injection. Dose escalation to 3.0 mg daily (or maximum tolerated dose)</description>
    <arm_group_label>Targeted Prescribing Pathway (LIRA 3mg + Standard Care)</arm_group_label>
    <other_name>Liraglutide 3mg</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Specialist Obesity Management Services</intervention_name>
    <description>Specialist Obesity Management Services standard of care</description>
    <arm_group_label>Standard Care</arm_group_label>
    <arm_group_label>Targeted Prescribing Pathway (LIRA 3mg + Standard Care)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  be aged between 18-75 years old (inclusive)&#xD;
&#xD;
          -  understand written and spoken English&#xD;
&#xD;
          -  be able to give in informed consent&#xD;
&#xD;
          -  a body mass index ≥35 kg/m2,&#xD;
&#xD;
          -  have been referred to Tier 3 weight management or equivalent service in one of the&#xD;
             five participating sites,&#xD;
&#xD;
          -  have a stable body weight (less than 5kg self-reported change during the previous 12&#xD;
             weeks),&#xD;
&#xD;
          -  Participant must be able to meet at least one of the inclusion criteria listed below:&#xD;
&#xD;
               1. prediabetes (defined as established diagnosis of impaired fasting glycaemia (IFG)&#xD;
                  from GP and/or established diagnosis of impaired glucose tolerance (IGT) from GP&#xD;
                  and/or HbA1C 42-47 mmol/mol (6-6.4%) without glucose lowering medications, at a&#xD;
                  blood test during the last 6 months) and/or&#xD;
&#xD;
               2. type 2 diabetes [defined as established diagnosis of Type II diabetes from GP&#xD;
                  and/or HbA1C ≥48 mmol/mol (&gt;6.5%) at a blood test during the last 6 months] being&#xD;
                  treated with any combination of lifestyle, metformin, sulphonylureas,&#xD;
                  thiazolidinediones (TZDs) or SGLT-2, and/or&#xD;
&#xD;
               3. hypertension treated (defined as being on antihypertensive treatment with or&#xD;
                  without a diagnosis of hypertension from GP) or untreated (defined as Systolic&#xD;
                  Blood Pressure (SBP) ≥140 mmHg at two consecutive visits at the Tier 3 clinic),&#xD;
                  and/or&#xD;
&#xD;
               4. obstructive sleep apnoea (on CPAP or established diagnosis of Apnoea Hypopnoea&#xD;
                  Index ≥15 at sleep studies during the last 12 months)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of Type 1 diabetes&#xD;
&#xD;
          -  Type 2 diabetes with treatment on DPP-IV or insulin currently&#xD;
&#xD;
          -  Treatment with GLP-1 receptor agonists within the last 6 months and/or have a history&#xD;
             of GLP-1 receptor agonist intolerance.&#xD;
&#xD;
          -  Treatment with anti-obesity drugs within the last 12 weeks prior to randomisation&#xD;
&#xD;
          -  eGFR ≤30ml/min/1.73m2 on serum testing over the last 26 weeks&#xD;
&#xD;
          -  Females referred to the clinic because of fertility problem&#xD;
&#xD;
          -  Females of child bearing potential who are pregnant, breast-feeding or intend to&#xD;
             become pregnant or are not using or willing to use adequate contraceptive methods&#xD;
             during the study period&#xD;
&#xD;
          -  Have terminal illness&#xD;
&#xD;
          -  Are not primarily responsible for their own care&#xD;
&#xD;
          -  Not willing or able to give informed consent&#xD;
&#xD;
          -  Any other significant disease or disorder which in the opinion of the investigator,&#xD;
             may either put the participants at risk or may influence the result of the study or&#xD;
             the participant's ability to participate&#xD;
&#xD;
          -  Untreated or uncontrolled hypothyroidism/hyperthyroidism defined as thyroid-&#xD;
             stimulating hormone &gt;6 mIU/liter or &lt;0.4 mIU/liter&#xD;
&#xD;
          -  Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial&#xD;
             medullary thyroid carcinoma (FMTC)&#xD;
&#xD;
          -  Personal history of non-familial medullary thyroid carcinoma&#xD;
&#xD;
          -  History of chronic pancreatitis or idiopathic acute pancreatitis&#xD;
&#xD;
          -  Amylase levels three times higher than the upper normal range&#xD;
&#xD;
          -  Obesity induced by other endocrinologic disorders (e.g. Cushing's Syndrome)&#xD;
&#xD;
          -  Current or history of treatment with medications that may cause significant weight&#xD;
             gain, within 12 weeks prior to screening, including systemic corticosteroids (except&#xD;
             for a short course of treatment, i.e. 7-10 days), atypical antipsychotic and mood&#xD;
             stabilizers (e.g. clozapine, olanzapine, valproic acid and its derivatives, and&#xD;
             lithium)&#xD;
&#xD;
          -  History of major depressive episode during the last 2 years&#xD;
&#xD;
          -  History of initiation of antidepressants during the last 12 weeks&#xD;
&#xD;
          -  Simultaneous participation in other clinical trials of investigational drugs,&#xD;
             lifestyle or physical activity interventions.&#xD;
&#xD;
          -  Previous surgical treatment for obesity (excluding liposuction if performed &gt;1 year&#xD;
             before trial entry)&#xD;
&#xD;
          -  History of other severe psychiatric disorders&#xD;
&#xD;
          -  History of known or suspected abuse of alcohol and/or narcotics&#xD;
&#xD;
          -  History of major depressive episode during the last 2 years&#xD;
&#xD;
          -  Simultaneous participation in other clinical trials of investigational drugs,&#xD;
             lifestyle or physical activity interventions. Patients will only be able to take part&#xD;
             following participation in a previous clinical trial after a wash-out period of 16&#xD;
             weeks.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Melanie Davies, Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Univesrity of Leicester</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St Vincent's University Hospital</name>
      <address>
        <city>Dublin</city>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NHS Greater Glasgow and Clyde West Glasgow Ambulatory Care Hospital</name>
      <address>
        <city>Glasgow</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals of Leicester NHS Trust, Leicester General Hospital</name>
      <address>
        <city>Leicester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Aintree</name>
      <address>
        <city>Liverpool</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guy's and St Thomas' NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Ireland</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>December 20, 2016</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 30, 2017</study_first_posted>
  <last_update_submitted>April 29, 2021</last_update_submitted>
  <last_update_submitted_qc>April 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity</mesh_term>
    <mesh_term>Weight Loss</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liraglutide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>February 27, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03036800
org study id: 0626
nct id: NCT03036800
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A two year, parallel, two group, open-label, real-world randomised controlled trial (RCT)
      design for subjects with severe and complex obesity who are referred to a Tier 3 or
      equivalent specialist weight management/obesity service. Participants will be randomised to
      receive 1) standard care (obesity-specialist care), or 2) targeted prescribing pathway
      (obesity-specialist care plus targeted use of Liraglutide 3.0mg [LIRA 3mg] with pre-specified
      stopping rules for the medication). The aim of the study is to compare the effectiveness,
      budget impact, and cost-effectiveness between the two groups in a real-world setting among
      otherwise largely unselected patients.
Summary of Trial Design A two year, parallel, two group, open-label, real-world, RCT design
      for patients with severe and complex obesity who are referred to a Tier 3 obesity service
      (including patients who are referred to a Tier 3 service as part of the bariatric surgery
      pathway). The total duration of participation will be 104 weeks (+/-2 weeks).

      The first 52 weeks of the study (after randomisation) will determine whether using the
      targeted prescribing pathway in a Tier 3 setting will result in more participants attaining
      ≥15% weight loss compared with standard care. The second 52 weeks of the study will assess
      whether patients who lose ≥15% of their baseline weight by the first 52 weeks are more likely
      to maintain ≥15% weight loss for another 52 weeks in the targeted prescribing pathway
      compared with standard care. Further, budget impact, cost-effectiveness, improvement in
      obesity-related co-morbidities, complementary aspects of safety, effectiveness, adherence,
      and treatment satisfaction of both treatment groups will be assessed and compared.

      Participants will be randomised in a 2:1 fashion to either the intervention (targeted
      prescribing pathway + standard care) or control (standard care) group (2 intervention: 1
      control). The control group will receive standard care in a specialist obesity service (Tier
      3 or equivalent), according to the best practice in each site and can include total or
      partial meal replacement strategies. The intervention group will receive the same standard
      care as the control group (i.e. according to the best practice in each site) plus all
      participants will initially receive LIRA with pre-specified stopping rules. The targeted
      prescribing pathway: participants who do not meet the definition of a 'early and good
      responder' (defined as achieving ≥5% weight loss at 16 weeks, ≥10% weight loss at 32 weeks
      and ≥15% weight loss at 52 weeks) will have their LIRA 3mg treatment stopped. It is important
      to note that all participants will be analysed in the group to which they are randomised; in
      particular, participants in the intervention group who stop receiving LIRA 3mg will remain in
      the intervention group and will continue to receive standard care for the remainder of the
      study as per the targeted prescribing pathway (albeit, the part of the pathway where LIRA 3mg
      is not prescribed; see Figure 1).

      The study is intentionally designed to reflect a pragmatic "real-world" scenario and each
      Tier 3 provider may require a different number of visits for their programme. However, study
      appointments for data collection, titration reviews, application of the stopping rules of
      LIRA 3mg, and dispensing will be standardised for all of the five sites.

      Intervention (Targeted Prescribing Pathway)

      The NHS Weight Management pathway is divided into four distinct tiers:

      Tier 1: health promotion Tier 2: lifestyle interventions Tier 3: specialist multidisciplinary
      weight management services Tier 4: bariatric surgery

      Across the UK, each region has a specialist Tier 3 obesity and/or weight management service
      or equivalent, usually referred to as Tier 3. This includes a clinician led multidisciplinary
      team approach, potentially including a specialist physician, nurse, dietician, psychologist,
      physiotherapist, etc. From this point forwards, Tier 3 specialist weight management and/or
      equivalent services will be referred to as 'Tier 3' throughout the remainder of this
      protocol.

      Participants in the intervention group will receive the same standard care as those in the
      control group, i.e. the best medical practice delivered by the Tier 3 service at each site.
      Additionally, at baseline, LIRA 3mg will be prescribed to all of the participants in the
      intervention group at a starting dose of 0.6mg daily. Dose escalation of Liraglutide will
      occur according to a pre-specified titration protocol, from 0.6mg to a maximum of 3.0mg
      daily. Liraglutide dose will be initiated at 0.6mg and then increased to 1.2mg in Week 2,
      1.8mg in Week 3, 2.4mg in Week 4, and 3.0mg in Week 5. Participants in the intervention group
      will be aware that the LIRA 3mg treatment may be stopped at various time points throughout
      the duration of the study and that continued use of LIRA 3mg is based upon their response to
      the treatment in terms of them achieving pre-defined weight loss targets at 16, 32 and 52
      weeks.. Specifically, participants in the intervention group will continue to be prescribed
      LIRA 3mg for the 104 week duration of the study, unless one of the following stopping rules
      applies:

        1. st stopping rule: After 16 weeks (± 14 days) on the medication, only those participants
           who have lost ≥5% of their baseline weight will be offered further treatment with LIRA
           3mg for another 16 weeks. Participants who have not met this weight loss target will
           have their LIRA 3mg treatment stopped but will still continue in the targeted
           prescribing pathway but will receive standard care only during the remainder of the
           study.

        2. nd stopping rule: After 32 weeks (± 14 days) on the medication, only those participants
           who have lost ≥10% of their baseline weight and are still on treatment with LIRA 3mg
           will be offered another 20 weeks on LIRA 3mg. Participants who have not met this weight
           loss target will have their LIRA 3mg treatment stopped but will still continue in the
           targeted prescribing pathway but will receive standard care only during the remainder of
           the study.

        3. rd stopping rule: After the first year of treatment (week 52; ± 14 days), only those
           participants who have lost ≥15% of their baseline weight and are still on treatment with
           LIRA 3mg will be offered another 52 weeks on LIRA 3mg. Participants who have not met
           this weight loss target will have their LIRA 3mg treatment stopped but will still
           continue in the targeted prescribing pathway but will receive standard care only during
           the remainder of the study.

      Participants who fail to reach the pre-defined weight-loss targets to continue LIRA 3mg
      treatment, or who choose to stop receiving LIRA 3mg, will continue to be offered the standard
      care provided by the Tier 3 service. These participants will still attend the Clinical Review
      Visits but not the additional visits for participants who are still on LIRA 3mg (e.g. Weeks
      65 & 91) because these visits will not be relevant to them; visits at Weeks 65 and 91 are
      intended to provide a new prescription of LIRA 3mg and to discuss adherence and any side
      effects;; see Appendices 2 & 3).

      Participants will remain routinely in the Tier 3 service in-line with NICE guidance
      throughout the duration of the research study. Participants may be offered treatment options
      within the duration of the study, including bariatric surgery, as per NICE guidance and
      according to the decision of the local Tier 3 Multidisciplinary Team. Participants who have
      undergone bariatric surgery after randomisation will only be included in the intention to
      treat (ITT) analysis. This decision was made because the proportion of participants
      undergoing bariatric surgery is likely to be unbalanced between the treatment groups (i.e.
      more participants in the control group are expected to have bariatric surgery than in the
      targeted prescribing pathway treatment group), and thus weight loss in these individuals
      could unduly influence the study results. Participants who have been prescribed and start
      anti-obesity medication (such as Orlistat) will be ineligible for LIRA 3mg treatment.

      Control (Standard Care) Participants in the control group will follow the best medical care
      provided by the Tier 3 service at the relevant site. This typically involves dietary advice
      to reduce energy intake (and may include a period of partial or total meal replacement),
      accompanied - if available - by a physical activity programme, both supported by behavioural
      change techniques with regular professional contacts. The nature of the standard care will
      vary between the different Tier 3 services at each site, as this is a pragmatic 'real-world'
      study. Clinician input will include the medical assessment of participants for severe and
      complicated obesity and the prescription of anti-obesity drugs (such as Orlistat) as per
      local Tier 3 service policy. As with the LIRA 3mg group those patients taking
      antihypertensive or antidepressant medication will be assessed and it will be at the
      clinician's discretion as to whether these medications are changed. Participants will remain
      routinely in the Tier 3 service in-line with NICE guidance throughout the duration of the
      research study. Participants may be offered treatment options within the duration of the
      study, including bariatric surgery, as per NICE guidance and according to the decision of the
      local Tier 3 Multidisciplinary Team.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Weight loss of ≥15% at 52 weeks
time frame: 52 weeks
description: The primary outcome of the study will be the proportion of participants with severe and complicated obesity achieving weight loss of ≥15% at 52 weeks with the use of a targeted prescribing pathway (i.e. use of LIRA 3mg according to a pre-specified protocol in combination with standard care provided in Tier 3 services) versus standard care alone in a Tier 3 service.
measure: Budget impact of a Tier 3 weight management service
time frame: 52 & 104 weeks
description: Cost of the proposed LIRA 3mg (as per protocol - e.g. actual dose taken = number of days taking study drug x daily cost of drug, or cost of total amount of study drug used)
Cost of visits to clinician for assessment and medication prescription during Specialist Weight Management Service programme
Cost of visits to dietician during Specialist Weight Management Service programme
Cost of visits to psychologist during Specialist Weight Management Service programme
Cost of physical activity physiologist/physiotherapist during Specialist Weight Management Service programme (if applicable)
Cost of Multidisciplinary Team (MDT) discussion in Specialist Weight Management Service
Cost of blood tests in Specialist Weight Management Service
Cost of consumables and goods
Cost of referral into Tier 4
measure: Estimated long-term cost-effectiveness
time frame: 104 weeks
description: Length of treatment with LIRA 3mg
Daily dose of LIRA 3mg (based on actual doses taken)
measure: Improving obesity-related comorbidities
time frame: 52 & 104 weeks
description: This will be assessed by the Kings College Obesity Staging (KCOS) score. The score is 0-3.
measure: Maintenance of ≥15% weight loss until 104 weeks (an additional 52 weeks)
time frame: 104 weeks
description: Proportion of participants maintaining weight loss of ≥15% among those who lost ≥15% at 52 weeks
measure: Patient adherence to treatment
time frame: 16, 32, 52 and 104 weeks
description: Study drug reconciliation
measure: Referral rates to other obesity interventions
time frame: 52 and 104 weeks
description: Number of participants referred to Tier 4 for bariatric surgery over the 104 weeks study period
measure: Safety related outcomes
time frame: 52 and 104 weeks
description: AE reporting
measure: Patient satisfaction
time frame: 52 and 104 weeks
description: Treatment Satisfaction Questionnaire for Medication (TSQM)
measure: Patient quality of life
time frame: 52 and 104 weeks
description: EuroQol five dimension scale (EQ5D) the minimum value is 0 and maximum is 100, low scores are a worse outcome and high scores are a better outcome.
measure: Weight (kg)
time frame: 16, 32, 52 and 104 weeks
description: Absolute change in weight from baseline Anthropometric measures: (Kg)
measure: Relative change in weight from baseline
time frame: 16, 32, 52 and 104 weeks
description: (% change in weight)
measure: Physical Activity
time frame: 52 and 104 weeks
description: International physical activity questionnaire (IPAQ- Long Form) there is not a scale, this is based on hours and minutes of physical activity. A higher number is a better outcome and a lower number is a worse outcome.
measure: Change in concomitant medications
time frame: Screening - 104 weeks
description: Concomitant medication reporting
measure: Medical History (including surgical history)
time frame: 52 and 104 weeks
description: Patient notes
measure: HSRUQ (Health service and resource uses questionnaire)
time frame: Screening, 52 and 104 weeks
description: Questionnaire
measure: Length of treatment with LIRA 3mg
time frame: 52 and 104 weeks
description: Days of treatment with LIRA 3mg
measure: Daily dose of LIRA 3mg (based on actual doses taken)
time frame: 52 and 104 weeks
description: Mg of liraglutide actually taken
measure: HbA1C
time frame: Screening, 32, 52 and 104 weeks
description: Biochemistry: IFCC (mmol/mol)
measure: Proportion of participants with normoglycaemia (defined as HbA1C <42.0 mmol/mol without glucose lowering medications)
time frame: Screening, 52 and 104 weeks
description: % percentage of the population in each group having normoglycaemia
measure: Proportion of participants with prediabetes (defined as HbA1C 42.0-47.9 mmol/mol without glucose lowering medications)
time frame: Screening, 52 and 104 weeks
description: % percentage of the population in each group having prediabetes
measure: Proportion of participants with diabetes (defined as HbA1C ≥48 mmol/mol or on glucose lowering medications)
time frame: Screening, 52 and 104 weeks
description: % percentage of the population in each group having type 2 diabetes
measure: Number of medications for management of type 2 diabetes
time frame: Screening, 52 and 104 weeks
description: Number
measure: Dose of medications for management of type 2 diabetes
time frame: Screening, 52 and 104 weeks
description: Medications for type 2 diabetes dose
measure: Class of medications for type 2 diabetes
time frame: Screening, 52 and 104 weeks
description: Medication class for type 2 diabetes
measure: Monitoring of Albumin- Creatinine Ratio (ACR) for patients with prediabetes, diabetes and hypertension.
time frame: Screening, 32, 52 and 104 weeks
description: (mg/mmol)
measure: Blood pressure
time frame: Screening - 104 weeks
description: (mmHg)
measure: Proportion of participants with hypertension (defined as patients on antihypertensive medications or systolic blood pressure>140mmHg)
time frame: Screening, 52 and 104 weeks
description: % percentage of the population in each group having hypertension
measure: Dose of antihypertensive medication
time frame: Screening, 52 and 104 weeks
description: Dose of medications for treatment of hypertension
measure: Class of antihypertensive medications
time frame: Screening, 52 and 104 weeks
description: Medication class for treatment of hypertension
measure: Number of anti-hypertensive medication
time frame: Screening, 52 and 104 weeks
description: Number
measure: Epworth score
time frame: Screening, 52 and 104 weeks
description: Questionnaire
measure: Stop Bang questionnaire
time frame: Screening, 52 and 104 weeks
description: Questionnaire
measure: Proportion of participants on CPAP
time frame: Screening, 52 and 104 weeks
description: % percentage of the population in each group on CPAP
measure: CPAP pressures for patients on variable pressures CPAP
time frame: screening, 52 and 104 weeks
description: Centimeters of water pressure (cm H20)
measure: Apnoea Hypopnea Index (AHI) for participants with sleep apnoea who cannot tolerate CPAP or for participants on fixed pressures CPAP
time frame: Screening, 52 and 104 weeks
description: Apnoea Hypopnea Index
measure: Oxygen desaturation index for participants with sleep apnoea who cannot tolerate CPAP or for participants on fixed pressures CPAP
time frame: Screening, 52 and 104 weeks
description: Oxygen desaturation Index
measure: Lipids
time frame: Screening, 32, 52 and 104 weeks
description: Biochemistry: Cholesterol (mmol/l), triglycerides (mmol/l), HDL cholesterol (mmol/l), LDL cholesterol (mmol/l), HDL ratio
measure: Dose of medication for dyslipidaemia
time frame: Screening, 52 and 104 weeks
description: Dose of medications for treatment of dyslipidaemia
measure: Class of medications for dyslipidaemia
time frame: Screening, 52 and 104 weeks
description: Medication class for treatment of dyslipidaemia
measure: Number of medications for dyslipidaemia
time frame: Screening, 52 and 104 weeks
description: Number
measure: King's College Obesity Staging System assessment
time frame: Screening, 52 and 104 weeks
description: Scoring System
measure: The number of participants who did or did not attend at least 70% of the scheduled appointments with the Specialist Weight Management Service (completers)
time frame: 52 and 104 weeks
description: Number
measure: The number of participants who had to stop treatment with LIRA 3mg because of adverse effects (targeted prescribing pathway only)
time frame: 52 and 104 weeks
description: Number
measure: The number of participants who stopped LIRA 3mg at 16 weeks after randomization
time frame: 16 weeks
description: Number
measure: The number of participants who stopped LIRA 3mg at 32 weeks after randomization
time frame: 32 weeks
description: Number
measure: The number of participants who stopped LIRA 3mg at 52 weeks after randomization
time frame: 52 weeks
description: Number
measure: The number of participants who completed 52 weeks of the Specialist Weight Management Service programme despite stopping LIRA 3mg at 16 weeks
time frame: 52 weeks
description: % percentage
measure: The number of participants who completed 52 weeks of the Specialist Weight Management Service programme despite stopping LIRA 3mg at 32 weeks
time frame: 52 weeks
description: % percentage
measure: The adherence of participants with LIRA 3mg (monitored through return of used pens and questionnaires) - Targeted prescribing pathway only
time frame: 16, 32, 52 and 104 weeks
description: % percentage
measure: The number of participants started on anti-obesity drugs
time frame: 16, 32, 52 and 104 weeks
description: Number
measure: The adherence of participants with other anti-obesity medications
time frame: 16, 32, 52 and 104 weeks
description: % percentage
measure: Gastrointestinal symptoms
time frame: Baseline, 52 and 104 weeks
description: Total number of gastrointestinal symptoms in each group
measure: Overall hypoglycaemia rate
time frame: Baseline, 52 and 104 weeks
description: % of patients who experience a hypoglycaemic event in each group
measure: Overall AE/SAE rate
time frame: Baseline, 52 and 104 weeks
description: Total number of AE/SAE in each group
measure: Rates of severe hypoglycaemia
time frame: Baseline, 52 and 104 weeks
description: % of patients who experience severe hypoglycaemia in each group
measure: Heart rate
time frame: Baseline - 104 weeks
description: Pulse/min
measure: Impact of Weight on Quality of Life-Lite (IWQOL-Lite)
time frame: Baseline, 52 and 104 weeks
description: The minimum value is 1 and maximum value is 5. A higher number is a worse outcome and a lower number is a better outcome.
measure: Patient Health Questionnaire-9 (PHQ9)
time frame: Baseline, 52 and 104 weeks
description: The minimum value is 0 and maximum value is 3. A higher number is a worse outcome and a lower number is a better outcome.
measure: Proportion of participants reaching weight loss of ≥5%, ≥10% and ≥15%
time frame: 16, 32, 52 (except of ≥15% weight loss which is primary outcome) and 104 weeks
description: (% percentage)
measure: BMI and change in BMI from baseline
time frame: 16, 32, 52 and 104 weeks
description: (kg/m2)
measure: Waist circumference
time frame: 52 and 104 weeks
description: (cm)
arm group label: Targeted Prescribing Pathway (LIRA 3mg + Standard Care)
arm group type: Experimental
description: Standard care plus targeted use of the intervention Liraglutide (LIRA) 3mg when pre-specified stopping rules for the medication apply
arm group label: Standard Care
arm group type: Active Comparator
description: standard Tier 3 obesity specialist service care
intervention type: Drug
intervention name: Saxenda
description: standard care plus targeted use of Liraglutide (LIRA) 3mg when pre-specified stopping rules for the medication apply. Liraglutide (Saxenda) 6 mg/mL solution for injection in pre-filled pen, administered by subcutaneous injection. Dose escalation to 3.0 mg daily (or maximum tolerated dose)
arm group label: Targeted Prescribing Pathway (LIRA 3mg + Standard Care)
other name: Liraglutide 3mg
intervention type: Other
intervention name: Specialist Obesity Management Services
description: Specialist Obesity Management Services standard of care
arm group label: Standard Care
arm group label: Targeted Prescribing Pathway (LIRA 3mg + Standard Care)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Melanie Davies, Prof
role: Principal Investigator
affiliation: Univesrity of Leicester
facility: 
facility: 
facility: 
facility: 
facility: 
country: Ireland
country: United Kingdom
responsible party type: Sponsor
mesh term: Obesity
mesh term: Weight Loss
mesh term: Liraglutide
sharing ipd: No
submitted: February 27, 2023