<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/NCT03236350</url>
  </required_header>
  <id_info>
    <org_study_id>SHF/CTG059/2016</org_study_id>
    <nct_id>NCT03236350</nct_id>
  </id_info>
  <brief_title>Remote Ischaemic Conditioning on Blood Pressure Control in Chronic Kidney Disease Patients</brief_title>
  <acronym>ERIC-BP-CKD</acronym>
  <official_title>The Effect of Remote Ischaemic Conditioning on Blood Pressure Control in Patients With Chronic Kidney Disease - the ERIC-BP-CKD Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Singapore General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Duke-NUS Graduate Medical School</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Singapore General Hospital</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>
      Chronic kidney disease (CKD) is one of the leading causes of death and disability in&#xD;
      Singapore and worldwide. Hypertension is commonly inadequately controlled in patients with&#xD;
      CKD and this is associated with CKD progression and cardiovascular complications. Daily&#xD;
      episodes of Remote ischaemic conditioning (termed chronic RIC or CRIC) using transient limb&#xD;
      ischaemia/reperfusion applied for 1 to 12 months have been shown to lower systemic blood&#xD;
      pressure (SBP), prevent stroke and reduce post-myocardial infarction left ventricular (LV)&#xD;
      remodelling in experimental and clinical studies. In the ERIC-BP-CKD feasibility and efficacy&#xD;
      study, we hypothesise that CRIC administered for 28 days will lower systemic blood pressure&#xD;
      and improve blood pressure control in patients with CKD and hypertension.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic kidney disease (CKD) is one of the leading causes of death and disability in&#xD;
      Singapore and worldwide. CKD patients often suffer with inadequately controlled hypertension,&#xD;
      the presence of which is associated with cardiovascular complications such as left&#xD;
      ventricular (LV) hypertrophy, cardiac failure, and stroke. As such, novel treatments are&#xD;
      required to improve blood pressure control in order to improve health outcomes in CKD&#xD;
      patients.&#xD;
&#xD;
      Remote ischaemic conditioning (RIC) using transient limb ischaemia/reperfusion has been shown&#xD;
      to protect the kidney and microvasculature in experimental and clinical studies, and daily&#xD;
      episodes of RIC (termed chronic RIC or CRIC) applied for 1 to 12 months have been shown to&#xD;
      lower systemic blood pressure (SBP), prevent stroke and reduce post-myocardial infarction&#xD;
      left ventricular (LV) remodelling in experimental and clinical studies. Whether CRIC can&#xD;
      reduce SBP in hypertensive patients with CKD is not known. In the ERIC-BP-CKD feasibility and&#xD;
      efficacy study, we hypothesise that CRIC administered for 28 days will lower systemic blood&#xD;
      pressure and improve blood pressure control in patients with CKD and hypertension.&#xD;
&#xD;
      In this study, subjects will be randomised in a 1:1 ratio to receive therapy from either the&#xD;
      active autoRIC® Device or identical sham autoRIC® Device.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 28, 2017</start_date>
  <completion_date type="Anticipated">June 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">March 31, 2020</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Systolic blood pressure</measure>
    <time_frame>Baseline and 28 days</time_frame>
    <description>Difference in change in systolic blood pressure (measured by automated office blood pressure recording) from baseline to after 28 days between CRIC versus sham control therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of antihypertensive medications</measure>
    <time_frame>Baseline and 28 days</time_frame>
    <description>Reduction in number of medications required for treating hypertension</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Central aortic systolic pressure</measure>
    <time_frame>Baseline and 28 days</time_frame>
    <description>Central aortic systolic pressure (measured by assessing the arterial waveform after 28 days of CRIC or sham control therapy).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Arterial pulse waveform</measure>
    <time_frame>Baseline and 28 days</time_frame>
    <description>The arterial pulse waveform (measured after 28 days of CRIC or sham control therapy).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LV systolic and diastolic function</measure>
    <time_frame>Baseline and 28 days</time_frame>
    <description>Change in LV systolic and diastolic function assessed by echocardiography from baseline following 28 days of CRIC or sham control therapy (subset of 20 patients).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LV wall thickness</measure>
    <time_frame>Baseline and 28 days</time_frame>
    <description>Change in LV wall thickness assessed by echocardiography from baseline following 28 days of CRIC or sham control therapy (subset of 20 patients).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spot Urine Protein-Creatinine Ratio</measure>
    <time_frame>Baseline and 28 days</time_frame>
    <description>Change in Proteinuria assessed by Spot Urine Protein-Creatinine Ratio from baseline after 28 days of CRIC or sham control therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum creatinine and eGFR</measure>
    <time_frame>Baseline and 28 days</time_frame>
    <description>Change in Renal function (assessed by serum creatinine and eGFR from baseline to after 28 days of CRIC or sham control therapy).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood biomarkers for CKD and inflammation</measure>
    <time_frame>Baseline and 28 days</time_frame>
    <description>CRP, IL-6, PAI-1, sCD40 ligand, and TNF-alpha will be measured for CKD and inflammation following 28 days of CRIC or sham control therapy.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">85</enrollment>
  <condition>Chronic Kidney Diseases</condition>
  <condition>Hypertension</condition>
  <condition>Cardiovascular Diseases</condition>
  <arm_group>
    <arm_group_label>CRIC Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>An autoRIC® Device will be placed on the upper arm daily to complete the preset protocol and will be repeated daily for 28 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Control</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>An autoRIC® Device visually identical to that used in the CRIC protocol will be placed on the upper arm daily to complete the preset protocol and will be repeated daily for 28 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Active autoRIC® (CRIC Treatment)</intervention_name>
    <description>The active autoRIC® Device is programmed to go through a preset protocol of inflation and deflation cycles every session. The sessions will be repeated daily for 28 days.</description>
    <arm_group_label>CRIC Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham Control autoRIC® (Sham Control)</intervention_name>
    <description>The Sham Control autoRIC® Device is visually identical to the active autoRIC® Device but the simulated protocol applied comprises of vibrations of the device but no inflation of the cuff every session. The sham device provides the same sound and vibration as that of the pump inflating and the same LED indicators on the Active Unit. The sessions will be repeated daily for 28 days.</description>
    <arm_group_label>Sham Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed informed consent&#xD;
&#xD;
          2. Aged 21 years and older&#xD;
&#xD;
          3. CKD (all stages 1-4)&#xD;
&#xD;
          4. On treatment for hypertension and automated office BP (AOBP) ≥ 140mmHg (this will be&#xD;
             determined by an automated oscillometric BP device)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with polycystic kidney disease&#xD;
&#xD;
          2. Atrial fibrillation&#xD;
&#xD;
          3. Patients on long-acting sulphonylureas (eg glibenclamide) or nicorandil (as these&#xD;
             medications may interfere with the protective effect of CRIC).&#xD;
&#xD;
          4. Patients recruited into another study which may impact on this study.&#xD;
&#xD;
          5. Symptomatic peripheral arterial disease affecting the upper limbs (given nature of&#xD;
             upper-limb CRIC protocol).&#xD;
&#xD;
          6. Renal transplant / Dialysis patients&#xD;
&#xD;
          7. Pregnant patients&#xD;
&#xD;
          8. Patients on any anti-coagulant medications (e.g. Warfarin)&#xD;
&#xD;
          9. For echo sub-study only: Prior myocardial infarction, BMI &gt; 30kg/m2, known severe&#xD;
             acrdiac valve disease, known severely impaired LVEF &lt;35%&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jason Choo, MBBS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Singapore General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jason Choo, MBBS</last_name>
    <phone>65 63214426</phone>
    <email>jason.choo@singhealth.com.sg</email>
  </overall_contact>
  <location>
    <facility>
      <name>Singapore General Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>169608</zip>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jason Choo, MBBS</last_name>
      <phone>65 63214436</phone>
    </contact>
    <investigator>
      <last_name>Jason Choo, MBBS</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Derek Hausenloy, MBChB, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <results_reference>
    <citation>Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res. 2008 Aug 1;79(3):377-86. doi: 10.1093/cvr/cvn114. Epub 2008 May 2.</citation>
    <PMID>18456674</PMID>
  </results_reference>
  <results_reference>
    <citation>Luca MC, Liuni A, McLaughlin K, Gori T, Parker JD. Daily ischemic preconditioning provides sustained protection from ischemia-reperfusion induced endothelial dysfunction: a human study. J Am Heart Assoc. 2013 Feb 22;2(1):e000075. doi: 10.1161/JAHA.112.000075.</citation>
    <PMID>23525419</PMID>
  </results_reference>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>July 25, 2017</study_first_submitted>
  <study_first_submitted_qc>July 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 1, 2017</study_first_posted>
  <last_update_submitted>September 19, 2019</last_update_submitted>
  <last_update_submitted_qc>September 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 23, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Chronic Kidney Disease</keyword>
  <keyword>Hypertension</keyword>
  <keyword>Cardiovascular Disease</keyword>
  <keyword>Central Aortic Systolic Pressure</keyword>
  <keyword>Proteinuria</keyword>
  <keyword>Remote Ischemic Conditioning</keyword>
  <keyword>Left Ventricular Hypertrophy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Cardiovascular Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03236350
org study id: SHF/CTG059/2016
nct id: NCT03236350
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Chronic kidney disease (CKD) is one of the leading causes of death and disability in
      Singapore and worldwide. Hypertension is commonly inadequately controlled in patients with
      CKD and this is associated with CKD progression and cardiovascular complications. Daily
      episodes of Remote ischaemic conditioning (termed chronic RIC or CRIC) using transient limb
      ischaemia/reperfusion applied for 1 to 12 months have been shown to lower systemic blood
      pressure (SBP), prevent stroke and reduce post-myocardial infarction left ventricular (LV)
      remodelling in experimental and clinical studies. In the ERIC-BP-CKD feasibility and efficacy
      study, we hypothesise that CRIC administered for 28 days will lower systemic blood pressure
      and improve blood pressure control in patients with CKD and hypertension.
Chronic kidney disease (CKD) is one of the leading causes of death and disability in
      Singapore and worldwide. CKD patients often suffer with inadequately controlled hypertension,
      the presence of which is associated with cardiovascular complications such as left
      ventricular (LV) hypertrophy, cardiac failure, and stroke. As such, novel treatments are
      required to improve blood pressure control in order to improve health outcomes in CKD
      patients.

      Remote ischaemic conditioning (RIC) using transient limb ischaemia/reperfusion has been shown
      to protect the kidney and microvasculature in experimental and clinical studies, and daily
      episodes of RIC (termed chronic RIC or CRIC) applied for 1 to 12 months have been shown to
      lower systemic blood pressure (SBP), prevent stroke and reduce post-myocardial infarction
      left ventricular (LV) remodelling in experimental and clinical studies. Whether CRIC can
      reduce SBP in hypertensive patients with CKD is not known. In the ERIC-BP-CKD feasibility and
      efficacy study, we hypothesise that CRIC administered for 28 days will lower systemic blood
      pressure and improve blood pressure control in patients with CKD and hypertension.

      In this study, subjects will be randomised in a 1:1 ratio to receive therapy from either the
      active autoRIC® Device or identical sham autoRIC® Device.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Systolic blood pressure
time frame: Baseline and 28 days
description: Difference in change in systolic blood pressure (measured by automated office blood pressure recording) from baseline to after 28 days between CRIC versus sham control therapy.
measure: Number of antihypertensive medications
time frame: Baseline and 28 days
description: Reduction in number of medications required for treating hypertension
measure: Central aortic systolic pressure
time frame: Baseline and 28 days
description: Central aortic systolic pressure (measured by assessing the arterial waveform after 28 days of CRIC or sham control therapy).
measure: Arterial pulse waveform
time frame: Baseline and 28 days
description: The arterial pulse waveform (measured after 28 days of CRIC or sham control therapy).
measure: LV systolic and diastolic function
time frame: Baseline and 28 days
description: Change in LV systolic and diastolic function assessed by echocardiography from baseline following 28 days of CRIC or sham control therapy (subset of 20 patients).
measure: LV wall thickness
time frame: Baseline and 28 days
description: Change in LV wall thickness assessed by echocardiography from baseline following 28 days of CRIC or sham control therapy (subset of 20 patients).
measure: Spot Urine Protein-Creatinine Ratio
time frame: Baseline and 28 days
description: Change in Proteinuria assessed by Spot Urine Protein-Creatinine Ratio from baseline after 28 days of CRIC or sham control therapy.
measure: Serum creatinine and eGFR
time frame: Baseline and 28 days
description: Change in Renal function (assessed by serum creatinine and eGFR from baseline to after 28 days of CRIC or sham control therapy).
measure: Blood biomarkers for CKD and inflammation
time frame: Baseline and 28 days
description: CRP, IL-6, PAI-1, sCD40 ligand, and TNF-alpha will be measured for CKD and inflammation following 28 days of CRIC or sham control therapy.
arm group label: CRIC Treatment
arm group type: Experimental
description: An autoRIC® Device will be placed on the upper arm daily to complete the preset protocol and will be repeated daily for 28 days.
arm group label: Sham Control
arm group type: Sham Comparator
description: An autoRIC® Device visually identical to that used in the CRIC protocol will be placed on the upper arm daily to complete the preset protocol and will be repeated daily for 28 days.
intervention type: Device
intervention name: Active autoRIC® (CRIC Treatment)
description: The active autoRIC® Device is programmed to go through a preset protocol of inflation and deflation cycles every session. The sessions will be repeated daily for 28 days.
arm group label: CRIC Treatment
intervention type: Device
intervention name: Sham Control autoRIC® (Sham Control)
description: The Sham Control autoRIC® Device is visually identical to the active autoRIC® Device but the simulated protocol applied comprises of vibrations of the device but no inflation of the cuff every session. The sham device provides the same sound and vibration as that of the pump inflating and the same LED indicators on the Active Unit. The sessions will be repeated daily for 28 days.
arm group label: Sham Control
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
last name: Jason Choo, MBBS
role: Principal Investigator
affiliation: Singapore General Hospital
last name: Jason Choo, MBBS
phone: 65 63214426
email: jason.choo@singhealth.com.sg
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Singapore
citation: Hausenloy DJ, Yellon DM. Remote ischaemic preconditioning: underlying mechanisms and clinical application. Cardiovasc Res. 2008 Aug 1;79(3):377-86. doi: 10.1093/cvr/cvn114. Epub 2008 May 2.
PMID: 18456674
citation: Luca MC, Liuni A, McLaughlin K, Gori T, Parker JD. Daily ischemic preconditioning provides sustained protection from ischemia-reperfusion induced endothelial dysfunction: a human study. J Am Heart Assoc. 2013 Feb 22;2(1):e000075. doi: 10.1161/JAHA.112.000075.
PMID: 23525419
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
mesh term: Hypertension
mesh term: Cardiovascular Diseases
sharing ipd: No