Remote Ischaemic Conditioning in STEMI Patients in AFRICA: The RIC-AFRICA Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1,400
- 试验地点
- 20
- 主要终点
- All-cause death and early post-MI heart failure
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •We will be recruiting 3 different strata of STEMI patients.
- •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).
- •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.
- •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/
排除标准
- •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:
- •severe active skin disease/burns on both arms; or
- •bilateral upper limb amputations; or
- •evidence of acute limb ischaemia on either arm; or
- •active upper limb gangrene of any digits;
- •breast cancer with lymph-node involvement on the ipsilateral side of RIC; or
- •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:
- •Compatible history with maximal chest pain between 24 -72 hours prior to presentation; and
- •Compatible biomarkers (elevated cardiac troponin); and
- •ECG compatible with recent STEMI; and/or
- •Compatible echocardiography.
- •Exclusion criteria
- •I. Refusal or inability to sign informed consent.
研究组 & 干预措施
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.
干预措施: Remote Ischaemic Conditioning (RIC) (Device)
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.
干预措施: Sham-control (Device)
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.
结局指标
主要结局
All-cause death and early post-MI heart failure
时间窗: 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.
次要结局
- Composite clinical endpoint for MACCE(30 days)
研究者
Mpiko Ntsekhe
Professor
University of Cape Town