Remote Ischaemic Conditioning in STEMI Patients in Sub-Saharan AFRICA

STEMI Clinical Trial

— RIC-AFRICA  

Official title:

Remote Ischaemic Conditioning in STEMI Patients in Sub-Saharan AFRICA: The RIC-AFRICA Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04813159
• Other study ID #: RIC AFRICA
• Status: Recruiting
• Phase: N/A
• Start date: January 12, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: June 2023
• Source: University of Cape Town
• Contact: Kishal Lukhna, MBChB
• Phone: +27732515380
• Email: kishallukhna[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 approximately 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.

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 approximately 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1200
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Ischemia
• Myocardial Reperfusion Injury
• Remote Ischaemic Conditioning
• Reperfusion Injury
• ST Elevation Myocardial Infarction
• STEMI

Intervention

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-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.

Locations

Country	Name	City	State
Kenya	Coast General Teaching Hospital	Mombasa
Kenya	Mombasa Hospital	Mombasa
Kenya	Kenyatta National Hospital	Nairobi
Kenya	Nairobi West hospital	Nairobi
South Africa	Groote Schuur Hospital	Cape Town	Western Cape
South Africa	Mitchell's Plain District Hospital	Cape Town	Western Cape
South Africa	Victoria Hospital	Cape Town	Western Cape
South Africa	Wentworth Hospital	Durban	KwaZulu Natal
South Africa	George Hospital	George	Western Cape
South Africa	Charlotte Maxeke Hospital	Johannesburg	Gauteng
South Africa	Tshepong Hospital	Klerksdorp	North West
Sudan	Al Saha Specialised Hospital	Khartoum	Khartoum State
Sudan	Al Shaab Teaching Hospital	Khartoum	Khartoum State
Sudan	Sudan Heart Centre	Khartoum	Khartoum State
Sudan	The Royal Care International Hospital	Khartoum
Sudan	Aliaa Specialist Hospital	Omdurman
Sudan	Medani Heart Centre	Wad Medani
Uganda	Uganda Heart Institute	Kampala

Sponsors (22)

Lead Sponsor

Collaborator

University of Cape Town

Al Saha Specialised Hospital, Sudan, Al Shaab Teaching Hospital, Sudan, Aliaa Specialist Hospital, Sudan, Charlotte Maxeke Hospital, South Africa, Coast General Teaching Hospital, Kenya, George Hospital, South Africa, Grey's Hospital, Groote Schuur Hospital, South Africa, Kenyatta National Hospital, Medani Heart Centre, Sudan, Mombasa Hospital, Kenya, Nairobi West Hospital, Kenya, Omdurman Hospital, Sudan, Royal Care international Hospital, Sudan, Sudan Heart Centre, Sudan, Tshepong Hospital, South Africa, Uganda Heart Institute, Universitas Academic Hospital, South Africa, University College, London, Victoria Hospital, South Africa, Wentworth Hospital, South Africa

Countries where clinical trial is conducted

Kenya,  South Africa,  Sudan,  Uganda, 

References & Publications (1)

Lukhna K, Hausenloy DJ, Ali AS, Bajaber A, Calver A, Mutyaba A, Mohamed AA, Kiggundu B, Chishala C, Variava E, Elmakki EA, Ogola E, Hamid E, Okello E, Gaafar I, Mwazo K, Makotoko M, Naidoo M, Abdelhameed ME, Badri M, van der Schyff N, Abozaid O, Xafis P, Giesz S, Gould T, Welgemoed W, Walker M, Ntsekhe M, Yellon DM. Remote Ischaemic Conditioning in STEMI Patients in Sub-Saharan AFRICA: Rationale and Study Design for the RIC-AFRICA Trial. Cardiovasc Drugs Ther. 2023 Apr;37(2):299-305. doi: 10.1007/s10557-021-07283-y. Epub 2021 Nov 5. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause death and early post-MI heart failure	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.	30 days
Secondary	Composite clinical endpoint for MACCE	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.	30 days