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.: PACTR202007518001972 Date of Registration: 16/07/2020
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title INVICTUS
Official scientific title INVestIgation of rheumatiC AF Treatment Using vitamin K antagonists, rivaroxaban or aspirin Studies
Brief summary describing the background and objectives of the trial This program is a comprehensive evaluation of RVHD, AF/flutter and stroke. It includes three major components 1. A multi-centre registry of RVHD 2. A prospective, randomized, parallel group, open-label clinical trial of rivaroxaban versus standard VKA therapy to evaluate non-inferiority of rivaroxaban to VKA, with testing for superiority if non-inferiority is satisfied. 3. A prospective, randomized, open-label superiority trial comparing rivaroxaban to aspirin in high risk patients either with AF and unsuitable for VKA or without AF and with high risk factors
Type of trial RCT
Acronym (If the trial has an acronym then please provide) INVICTUS
Disease(s) or condition(s) being studied Cardiology
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/01/2016
Actual trial start date 29/07/2016
Anticipated date of last follow up 01/12/2020
Actual Last follow-up date
Anticipated target sample size (number of participants) 4500
Actual target sample size (number of participants) 4565
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
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 Simple randomization using a randomization table created by a computer software program Central randomisation by phone/fax Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group rivaroxaban Rivaroxaban Arm - Rivaroxaban 20 mg once daily - Rivaroxaban 15 mg once daily (for patients with an creatinine clearance ≥15 and <50 ml/min) Expected follow up: average 4 years anticoagulant 2292
Control Group VKA depends on local availability expected follow up: average 4 years Any VKA approved for use in the participating country VKA titrated to achieve an INR of 2.0-3.0 2273 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Registry: Any patient with RVHD diagnosed by echocardiography (any age) Non-Inferiority Trial: 1. RVHD diagnosed by echocardiography at any time prior to enrollment 2. Age ≥18 3. Increased risk of stroke by any of the following a) CHA2DS2-VASc score ≥ 2 OR b) Moderate/Severe mitral stenosis with valve area ≤2.0 cm2 OR c) Left atrial spontaneous echo contrast OR d) Left atrial thrombus 4. Heart Rhythm a) AF or Flutter should be documented on baseline 12-lead ECG, or on a previous 12-lead ECG, Holter monitor, in-hospital ECG rhythm strip or Pacemaker or ICD electrogram. 1. Refusal to consent 2. Actively involved in any study that would compromise the protocol of INVICTUS Trial 3. Severe co-morbid condition with life expectancy < 1 year 4. Other serious condition(s) or logistic factors likely to interfere with study participation or with the ability to complete the trial, as appropriate to country or region. 5. Likely to have valve replacement surgery within 6 months 6. Mechanical valve prosthesis or other condition requiring treatment with VKAs. Patients with deep vein thrombosis or recent pulmonary embolism can be enrolled where both VKAs and rivaroxaban are approved. 7. Contraindication to the study medication of the trial a. Allergy to rivaroxaban b. Allergy to VKAs ( non-inferiority trial) c. Allergy to aspirin ( superiority trial) 8. Severe renal insufficiency with an calculated creatinine clearance (Cockcroft-Gault) < 15 ml/min 9. Serious bleeding in the past six months or at high risk for bleeding 10. Moderate to severe hepatic impairment 11. Ongoing need for dual antiplatelet therapy (patients with on-going aspirin therapy ≤100 mg per day are not excluded). 12. Ongoing need for dual strong inhibitors of CYP-3a4 or p-glycoprotein inhibitor. 13. Received an investigational drug in the past 30 days 14. Patients considered unsuitable for trial inclusion because of unwillingness to attend follow up visits 15. Women who are pregnant and/or breastfeeding 16. Women of child bearing age who do not use an effective form of birth control 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 19 Year(s) 96 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 17/12/2019 Hamilton Integrated Research Ethics Board
Ethics Committee Address
Street address City Postal code Country
293 Wellington Street North, Suite 102 Hamilton 1111 Canada
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome - Stroke(ischemic, hemorrhagic or undetermined type) - Systemic embolism at every visit, every 6 months
Secondary Outcome - Myocardial infarction - Hospitalization - Vascular death - Total Death - Composite of stroke, myocardial infarction, systemic embolism, vascular death at every visit, every 6 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Princess Marina Hospital Phologolo Extension 9 Gaborone Botswana
Hospital Alemo Oswaldo Cruz Avenue Doutor Dante Pazzanese 500 Sao Paulo Brazil
St. Elizabeth Catholic General Hospital Post Office Box 08, Kumbo, Northwest region Kumbo Cameroon
People Hospital of Peking University 11 Xizhimen South Avenue Beijing China
Beijing Anzhen Hospital 2 Anzhen Road, Chaoyang District Beijing China
Suez Canal University Hospital Ring Road Ismaelia Egypt
Jimma University Hospital Abajifar 1 Jimma Ethiopia
All India Institutes of Medical Sciences Ansari Nagar East, New Delhi Delhi India
Almaty Medical Institute 94 Tole Bi Street Almaty Kazakhstan
Kenyatta National Hospital Hospital Road Kenya Kenya
Kamuzu Central Hospital Lilongwe Road Lilongwe Malawi
Instituto Nacional de Cardiologia Ignacio Chavez Juan Badiano 1 Mexico City Mexico
Maputo Central Hospital Avenue Eduardo Mondlane Maputo Mozambique
BP Koirala Institute of Health Sciences Buddha Road Dharan Nepal
University College Hospital Queen Elizabeth Road Ibadan Nigeria
Agakhan University Hospital Stadium Road Karachi Pakistan
Hospital de Clinicas National University of Asuncion, Pedro Rodi 2139 Asuncion Paraguay
Philippine General Hospital 12 New Jersey Street Quezon City Philippines
Kigali University Teaching Hospital KN 4 Avenue Kigali Rwanda
Red Cross War Memorial Childrens Hospital Klipfontein and Milner Road Rondebosch South Africa
Alshaab Teaching Hospital Tabya Road Khartoum Sudan
MUHIMBILI UNIVERSITY OF HEALTH AND ALLIED SCIENCES United Nations Road Dar Es Salaam United Republic of Tanzania
Uganda Heart Institute Yusufu Lule Road Kampala Uganda
University Teaching Hospital Nationalist Road Lusaka Zambia
University of Zimbabwe 630 Churchill Avenue Harare Zimbabwe
FUNDING SOURCES
Name of source Street address City Postal code Country
Bayer AG 178 Muellerstrasse Berlin 13353 Germany
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Population Health Research Institute 20 Copeland Avenue Hamilton Canada University
COLLABORATORS
Name Street address City Postal code Country
Julia Molefe Baikai Phologolo Extension 9, Gaborone Gaborone Botswana
Alvaro Avezum Av. Doutor Dante Pazzanese, 500 Sao Paulo Brazil
Tantchou Tchoumi Jacques Cabral St. Elizabeth Hospital, Kumbo, Northwest region Kumbo Cameroon
Ma Changsheng 2 Anzhen Road, Chaoyang District Beijing China
Fathi Maklady Suez Canal University Hospital Ismaelia Egypt
Abraham Haileamlak Jimma University Hospital, Abajifar 1 Jimma Ethiopia
G. Karthikeyan All India Institute of Medical Sciences, Ansari Nagar East New Delhi India
Kairat Davletov 94 Tole Bi Street, Office 249 Almaty India
Bernard Gitura Kenyatta National Hospital, Hospital Road Nairobi Kenya
Lillian Gondwe Chunda Kamuzu Central Hospital Lilongwe Malawi
Jesus Antonio Gonzalez Hermosillo Instituto Nacional de Cardiologia Ignacio Chavez Mexico City Mexico
Albertino Damasceno Maputo Central Hospital, Avenue Eduardo Mondlane Maputo Mozambique
Sanjib Kumar Sharma BP Koirala Institute of Health Sciences Dharan Nepal
Okechukwu Ogah University College Hospital, Queen Elizabeth Road Ibadan Nigeria
Khawar Kazmi Cardiology Office, Stadium Road, Karachi Pakistan
Maria Paniagua Hospital de Clinicas Pedro Rodi 2139 Asuncion Pakistan
Antonio Miguel L. Dans 12 New Jersey Street Quezon City Philippines
Emmanuel Rusingiza Kamanzi University of Rwanda Kigali Rwanda
Liesl Zuhlke Klipfontein and Milner Road, Rondebosch Cape Town South Africa
Ahmed El Sayed Alshaab Teaching Hospital, Tabya Road Khartoum Sudan
Pilly Chillo MUHIMBILI UNIVERSITY, United Nations Road Dar Es Salaam United Republic of Tanzania
Peter Lwabi Mulago National Referral Hospital Kampala Uganda
John Musuku University Teaching Hospital, Nationalist Road Lusaka Zambia
James Hakim University of Zimbabwe, Avondale Harare Zimbabwe
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Stuart Connolly stuart.connolly@phri.ca 2892440315 20 Copeland Avenue
City Postal code Country Position/Affiliation
Hamilton Canada Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Salim Yusuf salim.yusuf@phri.ca 2892440315 20 Copland Avenue
City Postal code Country Position/Affiliation
Hamilton Canada Steering Committee Chair
Role Name Email Phone Street address
Scientific Enquiries Ganesan Karthikeyan karthik2010@gmail.com 919871074832 All India Institute of Medical Sciences
City Postal code Country Position/Affiliation
Delhi India Project Officer
Role Name Email Phone Street address
Public Enquiries Sumathy Rangarajan sumathy.rangarajan@phri.ca 9052965792 20 Copeland Avenue
City Postal code Country Position/Affiliation
Hamilton Canada Program Director
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual participant data that underlie the results reported in the article, after deidentification (text, tables, figures, and appendices) Study Protocol Beginning 9 months and ending 36 months following article publication Investigators whose proposed use of the data has been approved by an independent review committee. Type of analysis include: individual participant meta analysis.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://www.phri.ca/ Yes 22/02/2024 31/08/2022
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result - 22/02/2024
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information