Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202112803123592 Date of Approval: 02/12/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title RIC-AFRICA
Official scientific title Remote Ischaemic Conditioning in STEMI patients in sub-Saharan AFRICA: The RIC-AFRICA trial
Brief summary describing the background and objectives of the trial Background: Although remote ischaemic conditioning (RIC) has been shown to reduce myocardial infarct size in animal studies and ST-segment elevation myocardial infarction (STEMI) patients, it failed to improve clinical outcomes in the large CONDI-2/ERIC-PPCI trial. This may have been due to the low-risk patients recruited into the study and the fact that patients received optimal reperfusion therapy by primary percutaneous coronary intervention. In the RIC-AFRICA trial, we will investigate whether RIC can improve clinical outcomes in higher-risk STEMI patients in sub-Saharan Africa where reperfusion therapy is suboptimal. Study design: The RIC-AFRICA study is a sub-Saharan African multi-centre, randomized sham-controlled clinical trial designed to test the impact of RIC on the composite endpoint of 30-day mortality and heart failure in 1200 adult STEMI patients without access to PPCI. Randomized participants will be stratified by whether or not they receive thrombolytic therapy within 12 hours or arrive too late for thrombolytic therapy. Participants will receive either RIC (four 5-minute cycles of inflation [20mmHg above systolic blood pressure] and deflation of an upper arm cuff) or sham-control (similar protocol but with low-pressure inflation and deflation) within 1hour of thrombolysis and applied daily for the next 2 days. STEMI patients arriving greater than 24 hours after chest pain but within 72 hours will be recruited to participate in an observational arm. All participants will be telephonically contacted at 30 days to determine their outcome. Implications: The RIC-AFRICA trial will determine whether RIC can reduce rates of death and heart failure in higher-risk STEMI patients in sub-Saharan Africa where reperfusion therapy is suboptimal, thereby providing a low-cost, non-invasive therapy for improving health outcomes.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) RIC AFRICA
Disease(s) or condition(s) being studied Cardiology,Circulatory System
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Devices
Anticipated trial start date 06/12/2021
Actual trial start date 03/01/2022
Anticipated date of last follow up 01/02/2024
Actual Last follow-up date 01/02/2023
Anticipated target sample size (number of participants) 1200
Actual target sample size (number of participants) 1200
Recruitment status Active, not recruiting
Publication URL https://link.springer.com/article/10.1007/s10557-021-07283-y
Secondary Ids Issuing authority/Trial register
NCT04813159 U.S National Library of Medicine: Clinicaltrials.gov
DOH 27 092021 7608 South African National Clinical Trial Registry
HREC 1072021 Human Research Ethics Committee - University of Cape Town
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Remote Ischaemic Conditioning RIC The RIC blood pressure device will be placed on the upper arm for four 5-minute cycles, 40 minutes in total. The RIC protocol will be completed for four 5-minute cycles, 40 minutes in total, at recruitment and repeated daily over the next 2 days. The RIC protocol will comprise inflation of 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. 600
Control Group Sham control The sham protocol blood pressure cuff will be administrated for four 5-minute cycles of inflation and deflated for a further 5 minutes, for a total of 40 minutes. The sham protocol blood pressure cuff will be administrated for four 5-minute cycles and deflated for a further 5 minutes, for a total of 40 minutes and will be repeated daily for the next 2 days. 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. 600 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Eligible 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, i.e., ≥ 0.2mV in men ≥40 years (≥0.25 mV in men <40 years); 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. 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: a. compatible history with maximal chest pain between 24 and 72 hours prior to presentation; and b. compatible biomarkers (elevated cardiac troponin); and c. ECG compatible with recent STEMI; and/or d. compatible echocardiography. Interventional arm of the study: Randomized Control Trial Exclusion criteria I. STEMI patients undergoing primary percutaneous coronary intervention; II. STEMI patients presenting with cardiogenic shock or haemodynamic instability (systolic blood pressure (SBP) <90 mmHg for ≥30 minutes; or use of pharmacological and/or mechanical support to maintain SBP ≥ 90 mmHg; and evidence of end‐organ damage such as urine output of <30 mL/h; altered mental status; and/or serum lactate >2.0 mmol/L); III. Contra-indication to thrombolytic therapy in patients presenting within guideline-recommended time (<12 hours); IV. Conditions that preclude the use of RIC or sham-control on either arm such as: a. severe active skin disease/burns on both arms; or b. bilateral upper limb amputations; or c. evidence of acute limb ischaemia on either arm; or d. active upper limb gangrene of any digits; or e. bilateral arteriovenous fistulae needed for haemodialysis; or f. known breast cancer with ipsilateral lymph node involvement on the side of RIC; V. Inter-current disease with an expected life expectancy of less than 24 hours. Observational arm of the study Exclusion criteria I. Refusal or inability to sign informed consent. 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 105 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 10/09/2021 Human Research Ethics Committee Faculty of Health Sciences University of Cape Town
Ethics Committee Address
Street address City Postal code Country
Room G50, Old Main Building, Groote Schuur Hospital, Observatory, 7925 Cape Town 7925 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 23/03/2021 National Health Research Ethics Review Committee of Sudan
Ethics Committee Address
Street address City Postal code Country
Sudan Khartoum 00000 Sudan
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 10/09/2021 Research Ethics Committee Makerere University
Ethics Committee Address
Street address City Postal code Country
PO BOX 7072 Kampala, Uganda Kampala 7272 Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The primary composite endpoints of the study will be all-cause death and early post-MI heart failure, defined as a] pre-discharge (in-hospital) heart failure; or b] post-discharge heart failure hospitalization after index myocardial infarction at 30 days for patients discharged free of heart failure after their index MI admission. Pre-discharge heart failure will be defined as an event that meets the following criteria: I. new or worsening symptoms of heart failure; and II. objective clinical evidence of heart failure and fluid retention (such as crackles, raised JVP, S3 gallop or pedal oedema); or III. radiological evidence of pulmonary congestion/ oedema; or IV. increased cardiac biomarkers (such as BNP>500pg/mL or NT-proBNP>2,000pg/mL); and V. the initiation or augmentation of diuretic therapy. Heart failure hospitalization at 30 days will be defined as: I. an admission = 24 hours; and II. a diagnosis of heart failure made by the treating clinician; and III. the initiation or augmentation of diuretic therapy. 30-days post index myocardial infarction
Secondary Outcome 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 hospitalization. 30-days post index myocardial infarction
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Groote Schuur Hospital Anzo Road, Observatory Cape Town 7935 South Africa
Victoria Hospital Alphen Hill, Wynberg Cape Town 7800 South Africa
George Hospital Davidson Road George 6530 South Africa
Charlotte Maxeke Hospital Parktown Johannesburg 2193 South Africa
Universitas Academic Hospital Logeman Street Bloemfontein 9301 South Africa
Wentworth Hospital Boston Road KwaZulu Natal 4026 South Africa
Greys Hospital Town Hill Pietermaritzburg 3201 South Africa
Tshepong Hospital Jouberton Road Klerksdorp 2574 South Africa
Uganda Heart Institute Kampala Kampala 7272 Uganda
Coast General Teaching Hospital Mombasa Mombasa 80100 Kenya
Mombasa Hospital Mombasa Mombasa 80103 Kenya
Kenyatta National Hospital Nairobi Nairobi 00202 Kenya
Nairobi West Hospital Nairobi Nairobi 00202 Kenya
The Royal Care International Hospital Khartoum Khartoum 12217 Sudan
Aliaa Specialist Hospital Omdurman Omdurman 00000 Sudan
Omdurman Hospital Omdurman Omdurman 00000 Sudan
Medani Heart Centre Wad Madani Wad Madani 22213 Sudan
Al Shaab Teaching Hospital Khartoum Khartoum State 13315 Sudan
Sudan Heart Centre Khartoum Khartoum 14419 Sudan
Al Saha Specialised Hospital Khartoum Khartoum 13321 Sudan
FUNDING SOURCES
Name of source Street address City Postal code Country
University of Cape Town Division of Cardiology, University of Cape Town, Faculty of Health Sciences, Anzo Road, Observatory Cape Town 7295 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Cape Town Division of Cardiology, Groote Schuur Hospital, University of Cape Town, Faculty of Health Sciences Cape Town 7295 South Africa University
COLLABORATORS
Name Street address City Postal code Country
University College London 67 Chenies Mews London WC1E6HX United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Mpiko Ntsekhe mpiko.ntsekhe@uct.ac.za +27827754034 E17 Cardiac Clinic, Groote Schuur Hospital, Anzo Road, Observatory
City Postal code Country Position/Affiliation
Cape Town 7295 South Africa Head of Division of Cardiology Groote Schuur Hospital
Role Name Email Phone Street address
Public Enquiries Kishal Lukhna kishal.lukhna@uct.ac.za +27732515380 E17 Cardiac Clinic, Groote Schuur Hospital, Anzo Road, Observatory
City Postal code Country Position/Affiliation
Cape Town 7295 South Africa Clinical Cardiology Research Fellow
Role Name Email Phone Street address
Scientific Enquiries Derek Hausenloy d.hausenloy@ucl.ac.uk +6566015121 Hatter Cardiovascular Institute, 67 Chenies Mew
City Postal code Country Position/Affiliation
London WC1E6HX United Kingdom Professor and Signature Research Program Director in Cardiovascular and Metabolic Disorders
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes All participants who engage in the project will be consented for the use of their data in accordance with the parameters stated in the data management plan (including use in future research). The PI and trial steering committee will make a collaborative decision on whether data will be available for sharing to new interested scientific parties and determine the extent of data that will be uploaded onto UCT’s public data repository service. The PI will determine user access rights within the REDCap database according to study delegated roles and authorise access to potential new study investigators when needed. Informed Consent Form,Statistical Analysis Plan,Study Protocol 2 years after study completion The PI, together with the trial steering committee, will determine who will have access to study data.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://clinicaltrials.gov/ct2/show/NCT04813159 No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information