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Remote Ischaemic Conditioning in STEMI Patients in Sub-Saharan AFRICA (RIC-AFRICA)

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ClinicalTrials.gov Identifier: NCT04813159
Recruitment Status : Not yet recruiting
First Posted : March 24, 2021
Last Update Posted : September 20, 2021
Sponsor:
Collaborators:
Groote Schuur Hospital, South Africa
Uganda Heart Institute, Uganda
Mombasa Hospital, Kenya
Coast General Teaching Hospital, Kenya
Kenyatta National Hospital
Al Shaab Teaching Hospital, Sudan
Sudan Heart Centre, Sudan
Aliaa Specialist Hospital, Sudan
Medani Heart Centre, Sudan
Al Saha Specialised Hospital, Sudan
Omdurman Hospital, Sudan
Victoria Hospital, South Africa
George Hospital, South Africa
Charlotte Maxeke Hospital, South Africa
Tshepong Hospital, South Africa
Wentworth Hospital, South Africa
Grey's Hospital
Universitas Academic Hospital, South Africa
University College, London
Royal Care international Hospital, Sudan
Nairobi West Hospital, Kenya
Information provided by (Responsible Party):
Mpiko Ntsekhe, University of Cape Town

Brief Summary:
The RIC-AFRICA trial is a multi-centre, sham-controlled, double-blinded, randomised controlled trial (RCT) involving 1200 ST-segment elevation myocardial infarction (STEMI) patients presenting within ≤ 24 hours of myocardial infarction (MI) onset, across 20 sites in four sub-Saharan African countries (South Africa, Kenya, Sudan and Uganda). Patients presenting with STEMI and deemed ineligible for the RIC AFRICA RCT because they present >24 hours from MI onset but less than 72 hours, will be recruited into the observational arm of the study with the same endpoints as the trial. The purpose of the RCT is to determine whether Remote Ischaemic Conditioning (RIC) can reduce the rates of all-cause death and early post-myocardial heart failure at 30-days in STEMI patients treated predominantly with thrombolytic therapy.

Condition or disease Intervention/treatment Phase
STEMI Remote Ischaemic Conditioning Myocardial Reperfusion Injury Device: Remote Ischaemic Conditioning (RIC) Device: Sham-control Not Applicable

Detailed Description:

Background:

Remote ischaemic conditioning (RIC) using transient limb ischaemia and reperfusion has been shown to reduce myocardial infarct size in animal studies and small proof-of-concept clinical studies in ST-segment elevation myocardial infarction (STEMI) patients. However, RIC failed to improve clinical outcomes in the large European CONDI-2/ERIC-PPCI multi-centre randomised clinical trial. Potential reasons for this failure include the low-risk patients recruited into the study and the fact that patients received timely and optimal reperfusion therapy by primary percutaneous coronary intervention. The RIC-AFRICA trial will investigate whether RIC can improve clinical outcomes in higher-risk STEMI patients treated by thrombolysis in sub-Saharan Africa.

Study design:

The RIC-AFRICA trial is a multi-centre, sham-controlled, double-blinded, randomised controlled trial (RCT) involving 1200 ST-segment elevation myocardial infarction (STEMI) patients presenting within ≤ 24 hours of myocardial infarction (MI) onset, across 20 sites in four sub-Saharan African countries (South Africa, Kenya, Sudan and Uganda). Patients will be randomised to receive either RIC or sham control initiated prior to thrombolysis and applied daily for the next 2 days. The RIC protocol will comprise four 5-minute cycles of inflation (to 20mmHg above systolic blood pressure) and deflation of an automated pneumatic cuff placed on the upper arm. The sham control protocol will comprise four 5-minute cycles of low-pressure inflation (to 20mmHg) and deflation by a visually identical pneumatic cuff. The primary composite endpoint will be all-cause death and new-onset heart failure at 30-days post STEMI. Patients presenting with STEMI and deemed ineligible for the RIC AFRICA RCT because they present >24 hours from MI onset but less than 72 hours, will be recruited into the observational arm of the study with the same endpoints as the trial.

Implications:

The RIC-AFRICA trial will determine whether RIC can reduce rates of death and prevent heart failure in higher-risk STEMI patients treated by thrombolytic therapy in sub-Saharan Africa, thereby potentially providing a low-cost, non-invasive therapy for improving health outcomes.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Consented participants presenting with STEMI within 24 hours and who fulfil the study's eligibility criteria will be assigned a participant identification number and randomised to receive either RIC or sham control in a 1:1 ratio to ensure equal distribution amongst experimental arm. Randomisation will be conducted via a secure website and will be stratified by recruiting centre and patient stratum to ensure that a minimum of 2 participants in stratum 1 (eligible for thrombolysis and within <12 hours of MI onset) are recruited for every participant in stratum 2 (ineligible for thrombolysis because they present outside of guideline-recommended time (<12 hours) but presenting within 24 hours of most severe chest pain onset). The patient, treating clinician, study investigator and research team analysing the data will be blinded to the treatment allocation. Study intervention will be applied by the research nurse who will not have any further contact with the participant or trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The patient, treating clinician, study investigator and research team analysing the data will be blinded to the treatment allocation. Study intervention will be applied by the research nurse who will not have any further contact with the participant or trial.
Primary Purpose: Treatment
Official Title: Remote Ischaemic Conditioning in STEMI Patients in Sub-Saharan AFRICA: The RIC-AFRICA Trial
Estimated Study Start Date : October 2021
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : October 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Active Comparator: Remote Ischaemic Conditioning (RIC)
Consented STEMI participants presenting < 24 hours who are randomised to the RIC protocol, will receive blood pressure cuff inflation by the automated RIC blood pressure device to 20 mmHg above systolic blood pressure for 5 minutes and deflation for a further 5 minutes, a cycle which will be completed four times in total. The RIC protocol will be repeated daily for the next 2 days.
Device: Remote Ischaemic Conditioning (RIC)
The RIC protocol will comprise inflation of the automated RIC device to 20 mmHg above systolic blood pressure for 5 minutes and deflation for a further 5 minutes, a cycle which will be completed four times in total. The RIC protocol will be repeated daily for the next 2 days.

Sham Comparator: Sham-control
Consented STEMI participants presenting < 24 hours who are randomised to the sham protocol will receive low-pressure cuff inflation to 20 mmHg for 5 minutes and deflation for a further 5 minutes, a cycle which will be completed four times in total by a visually identical pneumatic cuff. The sham control protocol will be repeated daily for the next 2 days.
Device: Sham-control
The sham protocol will comprise low-pressure inflation to 20 mmHg for 5 minutes and deflation for a further 5 minutes, a cycle which will be completed four times in total by a visually identical pneumatic cuff used in the active arm. The sham control protocol will be repeated daily for the next 2 days.

No Intervention: Observational
Consented STEMI participants presenting > 24 hours but within 72 hours of MI onset will be recruited into the observational arm of the study which will have the same study endpoints as the RCT. These participants will not be randomised or receive any trial intervention.



Primary Outcome Measures :
  1. All-cause death and early post-MI heart failure [ Time Frame: 30 days ]
    The primary endpoint of the study will be a composite of all-cause death and early post-MI heart failure. The latter describes both a] pre-discharge (in-hospital) heart failure; or b] post discharge heart failure hospitalisation within 30 days for patients discharged free of heart failure after the index MI admission.


Secondary Outcome Measures :
  1. Composite clinical endpoint for MACCE [ Time Frame: 30 days ]
    Secondary outcome measures will include a composite clinical endpoint of MACCE at 30 days follow-up, defined as rates of (i) all-cause mortality; (ii) non-fatal myocardial infarction; (iii) transient ischaemic attack or stroke; and (iv) heart failure with or without hospitalisation.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

We will be recruiting 3 different strata of STEMI patients.

  1. Adult patients (≥18 years old) presenting with STEMI receiving thrombolytic therapy within guideline-recommended time (i.e., within <12 hours of most severe chest pain onset).
  2. Adult patients (≥18 years old) presenting with STEMI who are ineligible for thrombolysis because they present outside of guideline-recommended time (<12 hours) but within 24 hours of most severe chest pain onset.
  3. Adult patients (≥18 years old) presenting with evidence of STEMI who do not receive thrombolysis and who present ≥24 hours and within 72 hours of most severe chest pain onset.

Interventional arm of the Study: Randomized Control Trial

Patients who are deemed eligible for randomization into the trial on account of presentation with STEMI within 24 hours, will be eligible for the interventional arm of the study if the following inclusion/exclusion criteria are met.

Inclusion Criteria

I. Adult patients (≥18 years old) presenting with suspected STEMI (ST-elevation at the J-point in two contiguous leads ( ≥ 0.2mV in men or ≥ 0.15mV in women in leads V2-V3 and/or ≥ 0.1mV in other lead); and II. Within 24 hours of onset of myocardial infarction as deemed by the attending clinician; and III. Signed informed consent.

Exclusion criteria

I. STEMI patients due to undergo primary percutaneous coronary intervention;

II. STEMI patients presenting with cardiogenic shock or haemodynamic instability as defined by: systolic blood pressure (SBP) measurement of <90 mm Hg for ≥30 minutes; or use of pharmacological and/or mechanical support to maintain SBP ≥ 90 mm Hg; and evidence of end-organ damage defined by: urine output of <30 mL/h; altered mental status; and/or serum lactate >2.0 mmol/L;

III. Contraindications for the use of RIC or sham-control on either arm such as:

  1. severe active skin disease/burns on both arms; or
  2. bilateral upper limb amputations; or
  3. evidence of acute limb ischaemia on either arm; or
  4. active upper limb gangrene of any digits;
  5. breast cancer with lymph-node involvement on the ipsilateral side of RIC; or
  6. bilateral arteriovenous fistulae needed for haemodialysis.

IV. Inter-current disease with an expected life expectancy of less than 24 hours;

V. Contra-indication to thrombolytic therapy in patients presenting within guideline-recommended time (<12 hours).

Observational arm of the study

Patients who are deemed ineligible for randomization into the trial on account of presentation beyond 24 hours, will be eligible for the observational arm of the study if the following inclusion/exclusion criteria are met.

Inclusion Criteria

I. Signed informed consent; and

II. Clinical evidence of STEMI older than 24 hours and less than 72 hours as defined by:

  1. Compatible history with maximal chest pain between 24 -72 hours prior to presentation; and
  2. Compatible biomarkers (elevated cardiac troponin); and
  3. ECG compatible with recent STEMI; and/or
  4. Compatible echocardiography.

Exclusion criteria

I. Refusal or inability to sign informed consent.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04813159


Contacts
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Contact: Kishal Lukhna, MBChB +27732515380 kishallukhna@gmail.com
Contact: Sara Giesz +44(0)20 3447 9888 s.giesz@ucl.ac.uk

Locations
Show Show 20 study locations
Sponsors and Collaborators
University of Cape Town
Groote Schuur Hospital, South Africa
Uganda Heart Institute, Uganda
Mombasa Hospital, Kenya
Coast General Teaching Hospital, Kenya
Kenyatta National Hospital
Al Shaab Teaching Hospital, Sudan
Sudan Heart Centre, Sudan
Aliaa Specialist Hospital, Sudan
Medani Heart Centre, Sudan
Al Saha Specialised Hospital, Sudan
Omdurman Hospital, Sudan
Victoria Hospital, South Africa
George Hospital, South Africa
Charlotte Maxeke Hospital, South Africa
Tshepong Hospital, South Africa
Wentworth Hospital, South Africa
Grey's Hospital
Universitas Academic Hospital, South Africa
University College, London
Royal Care international Hospital, Sudan
Nairobi West Hospital, Kenya
Investigators
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Principal Investigator: Mpiko Ntsekhe, PhD University of Cape Town
Principal Investigator: Derek Hausenloy, PhD Hatter Cardiovascular Institute
Principal Investigator: Derek Yellon, PhD Hatter Cardiovascular Institute
Principal Investigator: Malcolm Walker, PhD Hatter Cardiovascular Institute
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Responsible Party: Mpiko Ntsekhe, Professor, University of Cape Town
ClinicalTrials.gov Identifier: NCT04813159    
Other Study ID Numbers: RIC AFRICA
First Posted: March 24, 2021    Key Record Dates
Last Update Posted: September 20, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Mpiko Ntsekhe, University of Cape Town:
Cardioprotection
Ischaemia/reperfusion injury
ST-Elevation myocardial infarction
Hospitalisation for post-myocardial infarction heart failure
Remote Ischaemic Conditioning
Cardiovascular mortality
STEMI
Additional relevant MeSH terms:
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ST Elevation Myocardial Infarction
Reperfusion Injury
Myocardial Reperfusion Injury
Ischemia
Pathologic Processes
Myocardial Infarction
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Infarction
Necrosis
Postoperative Complications
Cardiomyopathies