Myocardial Reperfusion Injury, Remote Ischaemic Conditioning, STEMI
Conditions
Keywords
Cardioprotection, Ischaemia/reperfusion injury, ST-Elevation myocardial infarction, Hospitalisation for post-myocardial infarction heart failure, Remote Ischaemic Conditioning, Cardiovascular mortality, STEMI
Brief summary
The RIC-AFRICA trial is a multi-centre, sham-controlled, randomised controlled trial (RCT) involving 1400 ST-segment elevation myocardial infarction (STEMI) patients presenting within ≤ 24 hours of myocardial infarction (MI) onset, across approximately 25 sites in 7 African countries (South Africa, Kenya, Sudan, Uganda, Mozambique, Senegal and Mauritius). 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.
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 Africa. Study design: The RIC-AFRICA trial is a multi-centre, sham-controlled, randomised controlled trial (RCT) involving 1400 ST-segment elevation myocardial infarction (STEMI) patients presenting within ≤ 24 hours of myocardial infarction (MI) onset, across approximately 20 sites in 7 African countries (South Africa, Kenya, Sudan, Uganda, Mozambique, Senegal and Mauritius). 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 Africa, thereby potentially providing a low-cost, non-invasive therapy for improving health outcomes.
Interventions
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.
DEVICESham-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.
Sponsors
Groote Schuur Hospital, South Africa
Uganda Heart Institute
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
University of Cape Town
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause death and early post-MI heart failure | 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
| Measure | Time frame | Description |
|---|---|---|
| Composite clinical endpoint for MACCE | 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. |
Countries
Kenya, Mozambique, Senegal, South Africa, Sudan, Uganda
Contacts
Primary ContactKishal Lukhna, MBChB
Backup ContactSara Giesz
Outcome results
None listed