<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/NCT02999412</url>
  </required_header>
  <id_info>
    <org_study_id>MEDBRIDGE</org_study_id>
    <nct_id>NCT02999412</nct_id>
  </id_info>
  <brief_title>Medication Reviews Bridging Healthcare: a Cluster-randomised Crossover Trial</brief_title>
  <acronym>MedBridge</acronym>
  <official_title>Medication Reviews Bridging Healthcare: a Cluster-randomised Crossover Trial to Study the Effects of Hospital-initiated Comprehensive Medication Reviews, Including Active Follow-up, on Elderly Patients' Healthcare Utilisation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Uppsala County Council, Sweden</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Region Gävleborg</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Västmanland County Council, Sweden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Uppsala University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Uppsala Clinical Research Center, Sweden</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Uppsala County Council, Sweden</source>
  <oversight_info>
    <has_dmc>No</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>
      Background: Mismanaged prescribing and use of medication among elderly puts major pressure on&#xD;
      current healthcare systems. Performing a medication review, a structured critical examination&#xD;
      of a patient's medications, during hospital stay with active follow-up into primary care&#xD;
      could optimise treatment benefit and minimise harm. However, a lack of high quality evidence&#xD;
      inhibits widespread implementation. This manuscript describes the rationale and design of a&#xD;
      pragmatic cluster-randomised, crossover trial to fulfil this need for evidence.&#xD;
&#xD;
      Aim: To study the effects of hospital-initiated comprehensive medication reviews, including&#xD;
      active follow-up, on elderly patients' healthcare utilisation compared to 1) usual care and&#xD;
      2) solely hospital based reviews.&#xD;
&#xD;
      Design: Multicentre, three-treatment, replicated, cluster-randomised, crossover trial.&#xD;
&#xD;
      Setting: 8 wards with a multidisciplinary team within 4 hospitals in 3 Swedish counties.&#xD;
&#xD;
      Participants: Patients aged 65 years or older, admitted to one of the study wards. Exclusion&#xD;
      criteria: Palliative stage; residing in other than the hospital's county; medication review&#xD;
      within the last 30 days; one-day admission.&#xD;
&#xD;
      Interventions: 1, comprehensive medication review during hospital stay; 2, same as 1 with the&#xD;
      addition of active follow-up into primary care; 3, usual care.&#xD;
&#xD;
      Primary outcome measure: Incidence of unplanned hospital visits during a 12-month follow-up&#xD;
      period.&#xD;
&#xD;
      Data collection and analyses: Extraction and collection from the counties' medical record&#xD;
      system into a GCP compliant electronic data capture system. Intention-to-treat-analyses using&#xD;
      log-linear Poisson generalized linear mixed models and frailty models.&#xD;
&#xD;
      Relevance: This study has a high potential to show a reduction in elderly patients'&#xD;
      morbidity, contributing to more sustainable healthcare in the long run.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background:&#xD;
&#xD;
      Mismanaged use of multiple medications is one of the greatest risks for healthcare-related&#xD;
      harm in the elderly and puts major pressure on current healthcare systems [1,2]. Identifying&#xD;
      effective interventions to optimise treatment benefit and minimise harm is an international&#xD;
      public health priority [3]. Comprehensive medication review, a structured and critical&#xD;
      examination of an individual patient's medications in relation to the patient's conditions,&#xD;
      aims to accomplish these goals [4]. A recently published Cochrane meta-analysis examined&#xD;
      whether medication reviews lead to improvement in health outcomes of hospitalised adult&#xD;
      patients compared with standard care [5]. Ten randomised controlled trials (RCTs) were&#xD;
      eventually used for analysis. The authors stated that they &quot;found no evidence that medication&#xD;
      review reduces mortality or hospital readmissions, although we did find evidence that&#xD;
      medication review may reduce emergency department contacts.&quot;[5] A beneficial or detrimental&#xD;
      effect on mortality or hospital admissions could be ruled out because estimates were&#xD;
      uncertain and follow-up was short. The authors stated that there is a strong need for RCTs of&#xD;
      high quality with at least one year follow-up and which are randomised at a cluster level to&#xD;
      minimise contamination bias [5]. In addition, a cluster randomised crossover design in which&#xD;
      each cluster serves as its own control would increase statistical power [6].&#xD;
&#xD;
      One of the included RCTs in this meta-analysis was conducted by our research group at Uppsala&#xD;
      University Hospital in 2005-2006 [7]. We demonstrated in this study that patients, aged 80&#xD;
      years or older, who received a comprehensive medication review including follow-up after&#xD;
      hospital discharge, performed by ward based clinical pharmacist, had 16% fewer hospital&#xD;
      revisits in the following year. The costs of hospital based care were approximately €200&#xD;
      lower per patient in the intervention group compared to the control group after the&#xD;
      intervention costs had been included. The study was conducted on two internal medicine wards&#xD;
      with 400 enrolled patients, all 80 years or older, which limits the generalisability of its&#xD;
      results.&#xD;
&#xD;
      Today, ten years after our previous RCT, several counties in Sweden have employed clinical&#xD;
      pharmacists who perform medication reviews in hospital settings. However, their way of&#xD;
      working has changed over time. For this reason it is important to identify the activities&#xD;
      that generate the greatest benefits to the patients, which can be done by performing a&#xD;
      pragmatic clinical trial, specifically designed to show the real-world effects of such&#xD;
      interventions [8]. Therefore we propose this pragmatic cluster-randomised, three-treatment,&#xD;
      crossover trial to study the effects of multidisciplinary medication reviews with active&#xD;
      follow-up after hospital discharge on elderly patients' healthcare utilisation, compared with&#xD;
      solely hospital based reviews and usual care. This large study will generate more robust&#xD;
      results and high external validity, with the potential to show effects on hard outcomes such&#xD;
      as healthcare utilisation. A similar study has, to our knowledge, not been undertaken&#xD;
      anywhere else in the world.&#xD;
&#xD;
      Aim:&#xD;
&#xD;
      To study the effects of hospital-initiated comprehensive medication reviews, including active&#xD;
      follow-up, on elderly patients' healthcare utilisation compared to 1) usual care and 2)&#xD;
      solely hospital based reviews.&#xD;
&#xD;
      Primary objectives:&#xD;
&#xD;
        1. The first primary objective is to test the hypothesis that the incidence of unplanned&#xD;
           hospital visits (admissions plus visits to the emergency department) among elderly&#xD;
           patients during a one year follow-up is lower, if they receive a comprehensive&#xD;
           medication review with active follow-up after discharge, than if they receive usual&#xD;
           care.&#xD;
&#xD;
        2. The second primary objective is to test the hypothesis that a comprehensive medication&#xD;
           review with active follow-up after discharge reduces the incidence of unplanned hospital&#xD;
           visits more than only a medication review during hospital stay compared to usual care.&#xD;
&#xD;
      Methods:&#xD;
&#xD;
      This study protocol has been developed by using the applicable recommendations of the SPIRIT&#xD;
      2013 Guidance for protocols of clinical trials, the Consort 2010 extension to cluster&#xD;
      randomised trials and the Consort 2010 extension to randomized trials of non-pharmacologic&#xD;
      treatment [9-11]. The full study protocol is attached to this trial registration.&#xD;
&#xD;
      Setting and clusters:&#xD;
&#xD;
      The study will be conducted in three counties in Sweden: Västmanland, Uppsala and Gävleborg.&#xD;
      Within these counties there will be four hospitals taking part in the study: Uppsala&#xD;
      University Hospital and the hospitals of Västerås, Enköping and Gävle. At these hospitals&#xD;
      clinical pharmacy, including the performance of medication reviews, is an established&#xD;
      practice or is planned to be implemented prior to the study. The intervention components of&#xD;
      the study will be performed by the existing workforce at two wards within each hospital. The&#xD;
      wards differ in terms of medical specialty: geriatric, internal medicine and stroke. All&#xD;
      wards are staffed with a multidisciplinary team consisting of physicians, nurses and clinical&#xD;
      pharmacists. The pharmacists have either followed a full-time one year post-graduate&#xD;
      programme in clinical pharmacy, in which the performance of medication reviews plays a&#xD;
      central role, or have followed undergraduate courses in clinical pharmacy and advanced&#xD;
      pharmacotherapy. Next to that, all pharmacists have at least six months working experience&#xD;
      with performing medication reviews in a multidisciplinary team. To assess clinical skill&#xD;
      performance related to medication reviews, all pharmacists participated in an objective&#xD;
      structured clinical examination (OSCE), prior to the start of the study. All pharmacists have&#xD;
      also participated in a training day with patient case discussions, to assure common practice&#xD;
      across all study sites. Other members of the ward team did not receive additional training.&#xD;
&#xD;
      In total eight wards will be included, with each ward acting as a cluster. The study will be&#xD;
      carried out as far as possible identically at the eight wards.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 6, 2017</start_date>
  <completion_date type="Actual">June 3, 2020</completion_date>
  <primary_completion_date type="Actual">December 11, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of unplanned hospital visits, extracted from the patients' electronic medical record</measure>
    <time_frame>12 months</time_frame>
    <description>Admissions plus visits to the emergency department</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Unplanned hospital admissions, extracted from the patients' electronic medical record</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned hospital admissions, extracted from the patients' electronic medical record</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned hospital admissions, extracted from the patients' electronic medical record</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned hospital admissions, extracted from the patients' electronic medical record</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emergency department visits, extracted from the patients' electronic medical record</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emergency department visits, extracted from the patients' electronic medical record</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emergency department visits, extracted from the patients' electronic medical record</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emergency department visits, extracted from the patients' electronic medical record</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned hospital visits, extracted from the patients' electronic medical record</measure>
    <time_frame>30 days</time_frame>
    <description>Admissions plus visits to the emergency department</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned hospital visits, extracted from the patients' electronic medical record</measure>
    <time_frame>3 months</time_frame>
    <description>Admissions plus visits to the emergency department</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned hospital visits, extracted from the patients' electronic medical record</measure>
    <time_frame>6 months</time_frame>
    <description>Admissions plus visits to the emergency department</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned medication-related hospital admissions, extracted from the patients' electronic medical record</measure>
    <time_frame>30 days</time_frame>
    <description>Two experienced clinicians will independently assess to what extent the hospital visits were medication-related using the WHO criteria for causality (certain, probable, possible and unlikely). This causality assessment will be based on Case Report Form (CRF) data in which treatment allocation has been blinded, and make use of validated algorithms such as the Naranjo algorithm and the Liverpool ADR Causality Assessment Tool. For a visit to be classified as medication-related consensus needs to be reached between the two clinicians, and where this is not possible, a third expert will have the deciding vote.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned medication-related hospital admissions, extracted from the patients' electronic medical record</measure>
    <time_frame>3 months</time_frame>
    <description>Two experienced clinicians will independently assess to what extent the hospital visits were medication-related using the WHO criteria for causality (certain, probable, possible and unlikely). This causality assessment will be based on Case Report Form (CRF) data in which treatment allocation has been blinded, and make use of validated algorithms such as the Naranjo algorithm and the Liverpool ADR Causality Assessment Tool. For a visit to be classified as medication-related consensus needs to be reached between the two clinicians, and where this is not possible, a third expert will have the deciding vote.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned medication-related hospital admissions, extracted from the patients' electronic medical record</measure>
    <time_frame>6 months</time_frame>
    <description>Two experienced clinicians will independently assess to what extent the hospital visits were medication-related using the WHO criteria for causality (certain, probable, possible and unlikely). This causality assessment will be based on Case Report Form (CRF) data in which treatment allocation has been blinded, and make use of validated algorithms such as the Naranjo algorithm and the Liverpool ADR Causality Assessment Tool. For a visit to be classified as medication-related consensus needs to be reached between the two clinicians, and where this is not possible, a third expert will have the deciding vote.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned medication-related hospital admissions, extracted from the patients' electronic medical record</measure>
    <time_frame>12 months</time_frame>
    <description>Two experienced clinicians will independently assess to what extent the hospital visits were medication-related using the WHO criteria for causality (certain, probable, possible and unlikely). This causality assessment will be based on Case Report Form (CRF) data in which treatment allocation has been blinded, and make use of validated algorithms such as the Naranjo algorithm and the Liverpool ADR Causality Assessment Tool. For a visit to be classified as medication-related consensus needs to be reached between the two clinicians, and where this is not possible, a third expert will have the deciding vote.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned primary care visits, extracted from the patients' electronic medical record</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned primary care visits, extracted from the patients' electronic medical record</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned primary care visits, extracted from the patients' electronic medical record</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unplanned primary care visits, extracted from the patients' electronic medical record</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from hospital discharge to first unplanned hospital visit, extracted from the patients' electronic medical record</measure>
    <time_frame>up to 12 months</time_frame>
    <description>time-to-event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Costs of hospital based care, extracted from the counties' costs per patient (CPP) system</measure>
    <time_frame>6 months</time_frame>
    <description>Costs for healthcare utilisation including the costs for the intervention. Costs for hospital based healthcare will be retrieved from the counties' CPP system, and average costs for clinical pharmacist employment will be calculated to account for the intervention costs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Costs of hospital based care, extracted from the counties' costs per patient (CPP) system</measure>
    <time_frame>12 months</time_frame>
    <description>Costs for healthcare utilisation including the costs for the intervention. Costs for hospital based healthcare will be retrieved from the counties' CPP system, and average costs for clinical pharmacist employment will be calculated to account for the intervention costs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality rates, extracted from the national death registry</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality rates, extracted from the national death registry</measure>
    <time_frame>3 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality rates, extracted from the national death registry</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality rates, extracted from the national death registry</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">2637</enrollment>
  <condition>Medication Review</condition>
  <arm_group>
    <arm_group_label>Comprehensive medication review (I1)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Comprehensive medication review with active follow-up (I2)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual care (Control)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Comprehensive medication review</intervention_name>
    <description>A thorough medication reconciliation, including a patient/carer interview, by a clinical pharmacist.&#xD;
The clinical pharmacist performs a comprehensive medication review in collaboration with the ward physician and patient, similar to a level three clinical medication review as earlier described in the literature [4]. This includes a structured, critical examination of all of the patient's medications in relation to the patient's conditions, based on information from the patient and the medical record. The objective is to optimise the impact of medications and minimizing the number of medication-related problems. The effects of medication changes will be monitored during the hospital stay by the physician or pharmacist, depending on the specific situation.&#xD;
Before discharge, the clinical pharmacist performs another medication reconciliation to check if the patient's prescriptions for medications to be used after hospital stay are consistent with the patient's medical record.</description>
    <arm_group_label>Comprehensive medication review (I1)</arm_group_label>
    <other_name>Intervention 1 (I1)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Comprehensive medication review with active follow-up</intervention_name>
    <description>The same as I1 but with the following additions:&#xD;
In case of any monitoring needs or necessary subsequent actions to be taken after hospital discharge, the clinical pharmacist and the ward physician send an electronic medication review referral to the patient's primary care physician upon discharge.&#xD;
A first phone call to the patient or carer is made by the clinical pharmacist 2-7 days after the patient is discharged depending on health condition and the pharmacist's availability. This phone call aims to ensure that all information has been understood correctly and to find out if any problems, concerns or questions have arisen after discharge.&#xD;
A second phone call will be made by the clinical pharmacist approximately 30 days after hospital discharge. This phone call aims to find out how the patient is managing the medication and if any problems, concerns or questions have arisen, and to provide the patient with a motivational &quot;boost&quot;.</description>
    <arm_group_label>Comprehensive medication review with active follow-up (I2)</arm_group_label>
    <other_name>Intervention 2 (I2)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Usual Care</intervention_name>
    <description>The control group will receive usual hospital care. According to Swedish legislation, usual care includes medication reconciliation upon admission. Next to that, the law requires a medication report addressing the patient's medication treatment to be given to the patient or carer upon hospital discharge and to be attached to the electronic discharge letter. This report contains a motivation and explanation to the changes in medication treatment that have been made during hospital stay, as well as the patient's updated medication list. These mandatory activities are currently carried out to various degree within the different hospitals and wards. Other activities as described in the interventions above may be carried out to a certain degree as well, but no clinical pharmacist will be involved.</description>
    <arm_group_label>Usual care (Control)</arm_group_label>
    <other_name>Control</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Admitted to one of the study wards&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has been subject to a medication review within the last 30 days as stated within their&#xD;
             medical record;&#xD;
&#xD;
          -  Residing in another than the hospital's county&#xD;
&#xD;
          -  Being in a palliative stage as stated in their medical record&#xD;
&#xD;
          -  Admitted for only one day&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ulrika Gillespie</last_name>
    <role>Study Chair</role>
    <affiliation>Uppsala University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Gävle Hospital</name>
      <address>
        <city>Gävle</city>
        <state>Gävleborg</state>
        <zip>80324</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Enköping Hospital</name>
      <address>
        <city>Enköping</city>
        <state>Uppsala Lan</state>
        <zip>74538</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uppsala University Hospital</name>
      <address>
        <city>Uppsala</city>
        <state>Uppsala Lan</state>
        <zip>75185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Västmanland Hospital</name>
      <address>
        <city>Västerås</city>
        <state>Västmanlands Lan</state>
        <zip>72334</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <link>
    <url>http://www.akademiska.se/MedBridge</url>
    <description>Official study website</description>
  </link>
  <reference>
    <citation>Kempen TGH, Bertilsson M, Lindner KJ, Sulku J, Nielsen EI, Hogberg A, Vikerfors T, Melhus H, Gillespie U. Medication Reviews Bridging Healthcare (MedBridge): Study protocol for a pragmatic cluster-randomised crossover trial. Contemp Clin Trials. 2017 Oct;61:126-132. doi: 10.1016/j.cct.2017.07.019. Epub 2017 Jul 21.</citation>
    <PMID>28739539</PMID>
  </reference>
  <reference>
    <citation>Kempen TGH, Hedstrom M, Olsson H, Johansson A, Ottosson S, Al-Sammak Y, Gillespie U. Assessment tool for hospital admissions related to medications: development and validation in older patients. Int J Clin Pharm. 2019 Feb;41(1):198-206. doi: 10.1007/s11096-018-0768-8. Epub 2018 Dec 26.</citation>
    <PMID>30585296</PMID>
  </reference>
  <results_reference>
    <citation>Kempen TGH, Kalvemark A, Gillespie U, Stewart D. Comprehensive medication reviews by ward-based pharmacists in Swedish hospitals: What does the patient have to say? J Eval Clin Pract. 2020 Feb;26(1):149-157. doi: 10.1111/jep.13121. Epub 2019 Mar 4.</citation>
    <PMID>30834647</PMID>
  </results_reference>
  <results_reference>
    <citation>Kempen TGH, Cam H, Kalvemark A, Lindner KJ, Melhus H, Nielsen EI, Sulku J, Gillespie U. Intervention fidelity and process outcomes of medication reviews including post-discharge follow-up in older hospitalized patients: Process evaluation of the MedBridge trial. J Clin Pharm Ther. 2020 Oct;45(5):1021-1029. doi: 10.1111/jcpt.13128. Epub 2020 Mar 14.</citation>
    <PMID>32171028</PMID>
  </results_reference>
  <results_reference>
    <citation>Kempen TGH, Kalvemark A, Sawires M, Stewart D, Gillespie U. Facilitators and barriers for performing comprehensive medication reviews and follow-up by multiprofessional teams in older hospitalised patients. Eur J Clin Pharmacol. 2020 Jun;76(6):775-784. doi: 10.1007/s00228-020-02846-8. Epub 2020 Feb 19.</citation>
    <PMID>32076745</PMID>
  </results_reference>
  <results_reference>
    <citation>Kempen TGH, Bertilsson M, Hadziosmanovic N, Lindner KJ, Melhus H, Nielsen EI, Sulku J, Gillespie U. Effects of Hospital-Based Comprehensive Medication Reviews Including Postdischarge Follow-up on Older Patients' Use of Health Care: A Cluster Randomized Clinical Trial. JAMA Netw Open. 2021 Apr 1;4(4):e216303. doi: 10.1001/jamanetworkopen.2021.6303. Erratum In: JAMA Netw Open. 2022 Apr 1;5(4):e229745.</citation>
    <PMID>33929523</PMID>
  </results_reference>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <last_update_submitted>June 21, 2021</last_update_submitted>
  <last_update_submitted_qc>June 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 25, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Uppsala County Council, Sweden</investigator_affiliation>
    <investigator_full_name>Thomas Kempen</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Integrated Healthcare System</keyword>
  <keyword>Inappropriate Prescribing</keyword>
  <keyword>Pragmatic Clinical Trial</keyword>
  <keyword>Crossover Design</keyword>
  <keyword>Randomised Controlled Trial</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan: Study Protocol with summarized SAP</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 20, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/12/NCT02999412/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan: Detailed Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 4, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/12/NCT02999412/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT02999412
org study id: MEDBRIDGE
nct id: NCT02999412
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Background: Mismanaged prescribing and use of medication among elderly puts major pressure on
      current healthcare systems. Performing a medication review, a structured critical examination
      of a patient's medications, during hospital stay with active follow-up into primary care
      could optimise treatment benefit and minimise harm. However, a lack of high quality evidence
      inhibits widespread implementation. This manuscript describes the rationale and design of a
      pragmatic cluster-randomised, crossover trial to fulfil this need for evidence.

      Aim: To study the effects of hospital-initiated comprehensive medication reviews, including
      active follow-up, on elderly patients' healthcare utilisation compared to 1) usual care and
      2) solely hospital based reviews.

      Design: Multicentre, three-treatment, replicated, cluster-randomised, crossover trial.

      Setting: 8 wards with a multidisciplinary team within 4 hospitals in 3 Swedish counties.

      Participants: Patients aged 65 years or older, admitted to one of the study wards. Exclusion
      criteria: Palliative stage; residing in other than the hospital's county; medication review
      within the last 30 days; one-day admission.

      Interventions: 1, comprehensive medication review during hospital stay; 2, same as 1 with the
      addition of active follow-up into primary care; 3, usual care.

      Primary outcome measure: Incidence of unplanned hospital visits during a 12-month follow-up
      period.

      Data collection and analyses: Extraction and collection from the counties' medical record
      system into a GCP compliant electronic data capture system. Intention-to-treat-analyses using
      log-linear Poisson generalized linear mixed models and frailty models.

      Relevance: This study has a high potential to show a reduction in elderly patients'
      morbidity, contributing to more sustainable healthcare in the long run.
Background:

      Mismanaged use of multiple medications is one of the greatest risks for healthcare-related
      harm in the elderly and puts major pressure on current healthcare systems [1,2]. Identifying
      effective interventions to optimise treatment benefit and minimise harm is an international
      public health priority [3]. Comprehensive medication review, a structured and critical
      examination of an individual patient's medications in relation to the patient's conditions,
      aims to accomplish these goals [4]. A recently published Cochrane meta-analysis examined
      whether medication reviews lead to improvement in health outcomes of hospitalised adult
      patients compared with standard care [5]. Ten randomised controlled trials (RCTs) were
      eventually used for analysis. The authors stated that they "found no evidence that medication
      review reduces mortality or hospital readmissions, although we did find evidence that
      medication review may reduce emergency department contacts."[5] A beneficial or detrimental
      effect on mortality or hospital admissions could be ruled out because estimates were
      uncertain and follow-up was short. The authors stated that there is a strong need for RCTs of
      high quality with at least one year follow-up and which are randomised at a cluster level to
      minimise contamination bias [5]. In addition, a cluster randomised crossover design in which
      each cluster serves as its own control would increase statistical power [6].

      One of the included RCTs in this meta-analysis was conducted by our research group at Uppsala
      University Hospital in 2005-2006 [7]. We demonstrated in this study that patients, aged 80
      years or older, who received a comprehensive medication review including follow-up after
      hospital discharge, performed by ward based clinical pharmacist, had 16% fewer hospital
      revisits in the following year. The costs of hospital based care were approximately €200
      lower per patient in the intervention group compared to the control group after the
      intervention costs had been included. The study was conducted on two internal medicine wards
      with 400 enrolled patients, all 80 years or older, which limits the generalisability of its
      results.

      Today, ten years after our previous RCT, several counties in Sweden have employed clinical
      pharmacists who perform medication reviews in hospital settings. However, their way of
      working has changed over time. For this reason it is important to identify the activities
      that generate the greatest benefits to the patients, which can be done by performing a
      pragmatic clinical trial, specifically designed to show the real-world effects of such
      interventions [8]. Therefore we propose this pragmatic cluster-randomised, three-treatment,
      crossover trial to study the effects of multidisciplinary medication reviews with active
      follow-up after hospital discharge on elderly patients' healthcare utilisation, compared with
      solely hospital based reviews and usual care. This large study will generate more robust
      results and high external validity, with the potential to show effects on hard outcomes such
      as healthcare utilisation. A similar study has, to our knowledge, not been undertaken
      anywhere else in the world.

      Aim:

      To study the effects of hospital-initiated comprehensive medication reviews, including active
      follow-up, on elderly patients' healthcare utilisation compared to 1) usual care and 2)
      solely hospital based reviews.

      Primary objectives:

        1. The first primary objective is to test the hypothesis that the incidence of unplanned
           hospital visits (admissions plus visits to the emergency department) among elderly
           patients during a one year follow-up is lower, if they receive a comprehensive
           medication review with active follow-up after discharge, than if they receive usual
           care.

        2. The second primary objective is to test the hypothesis that a comprehensive medication
           review with active follow-up after discharge reduces the incidence of unplanned hospital
           visits more than only a medication review during hospital stay compared to usual care.

      Methods:

      This study protocol has been developed by using the applicable recommendations of the SPIRIT
      2013 Guidance for protocols of clinical trials, the Consort 2010 extension to cluster
      randomised trials and the Consort 2010 extension to randomized trials of non-pharmacologic
      treatment [9-11]. The full study protocol is attached to this trial registration.

      Setting and clusters:

      The study will be conducted in three counties in Sweden: Västmanland, Uppsala and Gävleborg.
      Within these counties there will be four hospitals taking part in the study: Uppsala
      University Hospital and the hospitals of Västerås, Enköping and Gävle. At these hospitals
      clinical pharmacy, including the performance of medication reviews, is an established
      practice or is planned to be implemented prior to the study. The intervention components of
      the study will be performed by the existing workforce at two wards within each hospital. The
      wards differ in terms of medical specialty: geriatric, internal medicine and stroke. All
      wards are staffed with a multidisciplinary team consisting of physicians, nurses and clinical
      pharmacists. The pharmacists have either followed a full-time one year post-graduate
      programme in clinical pharmacy, in which the performance of medication reviews plays a
      central role, or have followed undergraduate courses in clinical pharmacy and advanced
      pharmacotherapy. Next to that, all pharmacists have at least six months working experience
      with performing medication reviews in a multidisciplinary team. To assess clinical skill
      performance related to medication reviews, all pharmacists participated in an objective
      structured clinical examination (OSCE), prior to the start of the study. All pharmacists have
      also participated in a training day with patient case discussions, to assure common practice
      across all study sites. Other members of the ward team did not receive additional training.

      In total eight wards will be included, with each ward acting as a cluster. The study will be
      carried out as far as possible identically at the eight wards.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Health Services Research
masking: Single (Outcomes Assessor)
measure: Incidence of unplanned hospital visits, extracted from the patients' electronic medical record
time frame: 12 months
description: Admissions plus visits to the emergency department
measure: Unplanned hospital admissions, extracted from the patients' electronic medical record
time frame: 30 days
measure: Unplanned hospital admissions, extracted from the patients' electronic medical record
time frame: 3 months
measure: Unplanned hospital admissions, extracted from the patients' electronic medical record
time frame: 6 months
measure: Unplanned hospital admissions, extracted from the patients' electronic medical record
time frame: 12 months
measure: Emergency department visits, extracted from the patients' electronic medical record
time frame: 30 days
measure: Emergency department visits, extracted from the patients' electronic medical record
time frame: 3 months
measure: Emergency department visits, extracted from the patients' electronic medical record
time frame: 6 months
measure: Emergency department visits, extracted from the patients' electronic medical record
time frame: 12 months
measure: Unplanned hospital visits, extracted from the patients' electronic medical record
time frame: 30 days
description: Admissions plus visits to the emergency department
measure: Unplanned hospital visits, extracted from the patients' electronic medical record
time frame: 3 months
description: Admissions plus visits to the emergency department
measure: Unplanned hospital visits, extracted from the patients' electronic medical record
time frame: 6 months
description: Admissions plus visits to the emergency department
measure: Unplanned medication-related hospital admissions, extracted from the patients' electronic medical record
time frame: 30 days
description: Two experienced clinicians will independently assess to what extent the hospital visits were medication-related using the WHO criteria for causality (certain, probable, possible and unlikely). This causality assessment will be based on Case Report Form (CRF) data in which treatment allocation has been blinded, and make use of validated algorithms such as the Naranjo algorithm and the Liverpool ADR Causality Assessment Tool. For a visit to be classified as medication-related consensus needs to be reached between the two clinicians, and where this is not possible, a third expert will have the deciding vote.
measure: Unplanned medication-related hospital admissions, extracted from the patients' electronic medical record
time frame: 3 months
description: Two experienced clinicians will independently assess to what extent the hospital visits were medication-related using the WHO criteria for causality (certain, probable, possible and unlikely). This causality assessment will be based on Case Report Form (CRF) data in which treatment allocation has been blinded, and make use of validated algorithms such as the Naranjo algorithm and the Liverpool ADR Causality Assessment Tool. For a visit to be classified as medication-related consensus needs to be reached between the two clinicians, and where this is not possible, a third expert will have the deciding vote.
measure: Unplanned medication-related hospital admissions, extracted from the patients' electronic medical record
time frame: 6 months
description: Two experienced clinicians will independently assess to what extent the hospital visits were medication-related using the WHO criteria for causality (certain, probable, possible and unlikely). This causality assessment will be based on Case Report Form (CRF) data in which treatment allocation has been blinded, and make use of validated algorithms such as the Naranjo algorithm and the Liverpool ADR Causality Assessment Tool. For a visit to be classified as medication-related consensus needs to be reached between the two clinicians, and where this is not possible, a third expert will have the deciding vote.
measure: Unplanned medication-related hospital admissions, extracted from the patients' electronic medical record
time frame: 12 months
description: Two experienced clinicians will independently assess to what extent the hospital visits were medication-related using the WHO criteria for causality (certain, probable, possible and unlikely). This causality assessment will be based on Case Report Form (CRF) data in which treatment allocation has been blinded, and make use of validated algorithms such as the Naranjo algorithm and the Liverpool ADR Causality Assessment Tool. For a visit to be classified as medication-related consensus needs to be reached between the two clinicians, and where this is not possible, a third expert will have the deciding vote.
measure: Unplanned primary care visits, extracted from the patients' electronic medical record
time frame: 30 days
measure: Unplanned primary care visits, extracted from the patients' electronic medical record
time frame: 3 months
measure: Unplanned primary care visits, extracted from the patients' electronic medical record
time frame: 6 months
measure: Unplanned primary care visits, extracted from the patients' electronic medical record
time frame: 12 months
measure: Time from hospital discharge to first unplanned hospital visit, extracted from the patients' electronic medical record
time frame: up to 12 months
description: time-to-event
measure: Costs of hospital based care, extracted from the counties' costs per patient (CPP) system
time frame: 6 months
description: Costs for healthcare utilisation including the costs for the intervention. Costs for hospital based healthcare will be retrieved from the counties' CPP system, and average costs for clinical pharmacist employment will be calculated to account for the intervention costs.
measure: Costs of hospital based care, extracted from the counties' costs per patient (CPP) system
time frame: 12 months
description: Costs for healthcare utilisation including the costs for the intervention. Costs for hospital based healthcare will be retrieved from the counties' CPP system, and average costs for clinical pharmacist employment will be calculated to account for the intervention costs.
measure: All-cause mortality rates, extracted from the national death registry
time frame: 30 days
measure: All-cause mortality rates, extracted from the national death registry
time frame: 3 months
measure: All-cause mortality rates, extracted from the national death registry
time frame: 6 months
measure: All-cause mortality rates, extracted from the national death registry
time frame: 12 months
arm group label: Comprehensive medication review (I1)
arm group type: Active Comparator
arm group label: Comprehensive medication review with active follow-up (I2)
arm group type: Active Comparator
arm group label: Usual care (Control)
arm group type: Other
intervention type: Procedure
intervention name: Comprehensive medication review
description: A thorough medication reconciliation, including a patient/carer interview, by a clinical pharmacist.
The clinical pharmacist performs a comprehensive medication review in collaboration with the ward physician and patient, similar to a level three clinical medication review as earlier described in the literature [4]. This includes a structured, critical examination of all of the patient's medications in relation to the patient's conditions, based on information from the patient and the medical record. The objective is to optimise the impact of medications and minimizing the number of medication-related problems. The effects of medication changes will be monitored during the hospital stay by the physician or pharmacist, depending on the specific situation.
Before discharge, the clinical pharmacist performs another medication reconciliation to check if the patient's prescriptions for medications to be used after hospital stay are consistent with the patient's medical record.
arm group label: Comprehensive medication review (I1)
other name: Intervention 1 (I1)
intervention type: Procedure
intervention name: Comprehensive medication review with active follow-up
description: The same as I1 but with the following additions:
In case of any monitoring needs or necessary subsequent actions to be taken after hospital discharge, the clinical pharmacist and the ward physician send an electronic medication review referral to the patient's primary care physician upon discharge.
A first phone call to the patient or carer is made by the clinical pharmacist 2-7 days after the patient is discharged depending on health condition and the pharmacist's availability. This phone call aims to ensure that all information has been understood correctly and to find out if any problems, concerns or questions have arisen after discharge.
A second phone call will be made by the clinical pharmacist approximately 30 days after hospital discharge. This phone call aims to find out how the patient is managing the medication and if any problems, concerns or questions have arisen, and to provide the patient with a motivational "boost".
arm group label: Comprehensive medication review with active follow-up (I2)
other name: Intervention 2 (I2)
intervention type: Procedure
intervention name: Usual Care
description: The control group will receive usual hospital care. According to Swedish legislation, usual care includes medication reconciliation upon admission. Next to that, the law requires a medication report addressing the patient's medication treatment to be given to the patient or carer upon hospital discharge and to be attached to the electronic discharge letter. This report contains a motivation and explanation to the changes in medication treatment that have been made during hospital stay, as well as the patient's updated medication list. These mandatory activities are currently carried out to various degree within the different hospitals and wards. Other activities as described in the interventions above may be carried out to a certain degree as well, but no clinical pharmacist will be involved.
arm group label: Usual care (Control)
other name: Control
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Ulrika Gillespie
role: Study Chair
affiliation: Uppsala University Hospital
facility: 
facility: 
facility: 
facility: 
country: Sweden
url: http://www.akademiska.se/MedBridge
description: Official study website
citation: Kempen TGH, Bertilsson M, Lindner KJ, Sulku J, Nielsen EI, Hogberg A, Vikerfors T, Melhus H, Gillespie U. Medication Reviews Bridging Healthcare (MedBridge): Study protocol for a pragmatic cluster-randomised crossover trial. Contemp Clin Trials. 2017 Oct;61:126-132. doi: 10.1016/j.cct.2017.07.019. Epub 2017 Jul 21.
PMID: 28739539
citation: Kempen TGH, Hedstrom M, Olsson H, Johansson A, Ottosson S, Al-Sammak Y, Gillespie U. Assessment tool for hospital admissions related to medications: development and validation in older patients. Int J Clin Pharm. 2019 Feb;41(1):198-206. doi: 10.1007/s11096-018-0768-8. Epub 2018 Dec 26.
PMID: 30585296
citation: Kempen TGH, Kalvemark A, Gillespie U, Stewart D. Comprehensive medication reviews by ward-based pharmacists in Swedish hospitals: What does the patient have to say? J Eval Clin Pract. 2020 Feb;26(1):149-157. doi: 10.1111/jep.13121. Epub 2019 Mar 4.
PMID: 30834647
citation: Kempen TGH, Cam H, Kalvemark A, Lindner KJ, Melhus H, Nielsen EI, Sulku J, Gillespie U. Intervention fidelity and process outcomes of medication reviews including post-discharge follow-up in older hospitalized patients: Process evaluation of the MedBridge trial. J Clin Pharm Ther. 2020 Oct;45(5):1021-1029. doi: 10.1111/jcpt.13128. Epub 2020 Mar 14.
PMID: 32171028
citation: Kempen TGH, Kalvemark A, Sawires M, Stewart D, Gillespie U. Facilitators and barriers for performing comprehensive medication reviews and follow-up by multiprofessional teams in older hospitalised patients. Eur J Clin Pharmacol. 2020 Jun;76(6):775-784. doi: 10.1007/s00228-020-02846-8. Epub 2020 Feb 19.
PMID: 32076745
citation: Kempen TGH, Bertilsson M, Hadziosmanovic N, Lindner KJ, Melhus H, Nielsen EI, Sulku J, Gillespie U. Effects of Hospital-Based Comprehensive Medication Reviews Including Postdischarge Follow-up on Older Patients' Use of Health Care: A Cluster Randomized Clinical Trial. JAMA Netw Open. 2021 Apr 1;4(4):e216303. doi: 10.1001/jamanetworkopen.2021.6303. Erratum In: JAMA Netw Open. 2022 Apr 1;5(4):e229745.
PMID: 33929523
responsible party type: Principal Investigator
investigator affiliation: Uppsala County Council, Sweden
investigator full name: Thomas Kempen
investigator title: Principal Investigator
sharing ipd: No
provided document: 
provided document: 