INVestIgation of rheumatiC AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies, Non-Inferiority
- Conditions
- Rheumatic Heart Disease
- Interventions
- Drug: Rivaroxaban (20 mg)Drug: Vitamin K antagonists (VKA)
- Registration Number
- NCT02832544
- Lead Sponsor
- Population Health Research Institute
- Brief Summary
This program is a comprehensive evaluation of rheumatic valvular heart disease (RVHD), Atrial fibrillation (AF)/flutter and stroke.
A prospective, randomized, parallel group, open-label clinical trial of rivaroxaban versus standard vitamin K antagonists (VKA) therapy to evaluate non-inferiority of rivaroxaban to VKA, with testing for superiority if non-inferiority is satisfied.
- Detailed Description
Non-Inferiority Trial of rivaroxaban versus VKAs: 4,500 patients
Inclusion Criteria:
1. RVHD diagnosed by echocardiography at any time prior to enrollment
2. Age ≥18
3. Increased risk of stroke by any of the following
1. CHA2DS2-VASc score ≥ 2 OR
2. Moderate/Severe mitral stenosis with valve area ≤2.0 cm2 OR
3. Left atrial spontaneous echo contrast OR
4. 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.
Treatment:
Patients will be randomized either to receive rivaroxaban or any approved VKA. Treatment will be open-label.
1. Rivaroxaban Arm
* Rivaroxaban 20 mg once daily
* Rivaroxaban 15 mg once daily (for patients with an creatinine clearance ≥15 and \<50 ml/min)
2. VKA Arm
* Any VKA approved for use in the participating country
* VKA titrated to achieve an INR of 2.0-3.0
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 4565
-
RVHD diagnosed by echocardiography at any time prior to enrollment
-
Age ≥18
-
Increased risk of stroke by any of the following
- CHA2DS2-VASc score ≥ 2 OR
- Moderate/Severe mitral stenosis with valve area ≤2.0 cm2 OR
- Left atrial spontaneous echo contrast OR
- Left atrial thrombus
-
Heart Rhythm *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.
-
Refusal to give informed consent
-
Actively involved in any study that would compromise the protocol of INVICTUS Trial
-
Severe co-morbid condition with life expectancy < 1 year
-
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.
-
Likely to have valve replacement surgery within 6 months
-
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.
-
Contraindication to the study medication of the trial
- Allergy to rivaroxaban
- Allergy to VKAs ( non-inferiority trial)
- Allergy to aspirin ( superiority trial)
-
Severe renal insufficiency with an calculated creatinine clearance (Cockcroft-Gault) <15 ml/min
-
Serious bleeding in the past six months or at high risk for bleeding
-
Moderate to severe hepatic impairment
-
Ongoing need for dual antiplatelet therapy (patients with on-going aspirin therapy ≤100 mg per day are not excluded)
-
Ongoing need for dual strong inhibitors of CYP-3a4 or p-glycoprotein inhibitor.
-
Received an investigational drug in the past 30 days
-
Patients considered unsuitable for trial inclusion because of unwillingness to attend follow up visits
-
Women who are pregnant and/or breastfeeding
-
Women of child bearing age who do not use an effective form of birth control.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rivaroxaban (20 mg) Rivaroxaban (20 mg) Rivaroxaban 20 mg od (n \~ 2250); 15 mg od (once daily) in patients with creatinine clearance (CrCl) 15-49 ml/min Vitamin K antagonists (VKA) Vitamin K antagonists (VKA) Any approved VKA in the participating country (n \~ 2250); VKA titrated to achieve an INR of 2.0-3.0
- Primary Outcome Measures
Name Time Method Time from randomization to the first occurrence of vascular death or death of unknown cause, stroke, myocardial infarction or systemic embolism Approximately 4 years Vascular death or death of unknown cause, stroke, myocardial infarction or systemic embolism
- Secondary Outcome Measures
Name Time Method Time from randomization to the first occurrence of composite of stroke or systemic embolism Approximately 4 years Composite of stroke or systemic embolism
Trial Locations
- Locations (139)
Beni Suef University Hospital
🇪🇬Banī Suwayf, Egypt
Zagazig University Hospital
🇪🇬Zagazig, Egypt
King George's Medical College
🇮🇳Lucknow, Uttar Pradesh, India
Sanjay Gandhi Post Graduate Institute of Medical Sciences
🇮🇳Lucknow, Uttar Pradesh, India
Moi Teaching and Referral Hospital
🇰🇪Eldoret, Kenya
Clinical Hospital of administrative department of President and Government of Kyrgyz Republic
🇰🇬Bishkek, Kyrgyzstan
BP Koirala Institute of Health Sciences
🇳🇵Dharān Bāzār, Nepal
Manmohan Cardiothoracic Vascular and Trasplant Center, IOM, TU
🇳🇵Kathmandu, Nepal
Manipal College of Medical Sciences
🇳🇵Pokhara, Nepal
Instituto Nacional de Cardiología
🇵🇾Asunción, Paraguay
Hospital Nacional Itaugua
🇵🇾Itaugua, Paraguay
Ndola Central Hospital
🇿🇲Ndola, Zambia
Via Médica Centro Clínico Barroso e Sebba Ltda
🇧🇷Goiania, Brazil
St. Elizabeth Catholic General Hospital, Cardiac Centre
🇨🇲Kumbo, Cameroon
Instituto do Coração - HCFMUSP
🇧🇷São Paulo, Brazil
Instituto Dante Pazzanese de Cardiologia
🇧🇷São Paulo, Brazil
Clinique Coeur Et Vie
🇨🇲Douala, Cameroon
Mehallah Rheumatic Heart Center
🇪🇬El Mansura, Egypt
Red Crescent Hospital
🇪🇬Tanta, Egypt
Douala General Hospital
🇨🇲Douala, Cameroon
Hopital Central Yaounde
🇨🇲Yaounde, Cameroon
Sohag University, Sohag
🇪🇬Sohag, Egypt
Zhongmou County People's Hospital
🇨🇳Henan, China
Ain Shams University Hospital
🇪🇬Cairo, Egypt
Instituto de Pesquisa Clínica de Campinas
🇧🇷Campinas, Brazil
LOEMA - Instituto de Pesquisa Clínica & Consultores Ltda
🇧🇷Campinas, Brazil
El Minia University Hospital
🇪🇬Minya, Egypt
Kazakh National Medical Institute,
🇰🇿Almaty, Kazakhstan
Karen Hospital
🇰🇪Nairobi, Kenya
University of Rwanda, Kigali University Teaching Hospital
🇷🇼Kigali, Rwanda
Alshaab Teaching Hospital
🇸🇩Khartoum, Sudan
Digna Prince Hospital
🇸🇩Port Sudan, Sudan
Suqian Peaple's Hospital of Nanjing Drum-Tower Hospital Group
🇨🇳Suqian, Jiangsu, China
The First Affiliated Hospital of Dalian Medical University
🇨🇳Dalian, Liaoning, China
Pi County People's Hospital
🇨🇳Chengdu, Sichuan, China
Anyue County People's Hospital
🇨🇳Ziyang, Sichuan, China
Wendeng Central Hospital
🇨🇳Weihai, Wendeng, China
Ningxia Peple's Hospital
🇨🇳Yinchuan, Ningxia, China
Zhengzhou 9th People's Hospital
🇨🇳Henan, China
Guangshan County People's Hospital
🇨🇳Henan, China
Queen Elizabeth Central Hospital
🇲🇼Blantyre, Malawi
Mzuzu Central Hospital
🇲🇼Mzuzu, Malawi
Kumuzu Central Hospital
🇲🇼Lilongwe, Malawi
Uganda Heart Institute
🇺🇬Kampala, Uganda
Cardresearch - Cardiologia Assistencial e de Pesquisa
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Dr. Ram Manohar Lohia Hospital @ PGIMER
🇮🇳New Delhi, Delhi, India
Nucleo de Estudios Clinicos - Universidade Federal do Triângulo Mineiro
🇧🇷Uberaba, Minas Gerais, Brazil
Hospital Angeles León
🇲🇽León, Guanajuato, Mexico
Eurolatino Pesquisas Médicas Ltda
🇧🇷Uberlândia, Minas Gerais, Brazil
Centro para el Desarrollo de la Medicina y Asistencia Especializada S.C.
🇲🇽Culiacan, Sinaloa, Mexico
All India Institute of Medical Sciences
🇮🇳New Delhi, Delhi, India
SMS Medical College
🇮🇳Jaipur, Rajasthan, India
Princess Marina Hospital
🇧🇼Gaborone, Botswana
Clínica Procardio Ltda.
🇧🇷Blumenau, Santa Catarina, Brazil
Fundação Faculdade de Medicina de São José do Rio Preto
🇧🇷São José do Rio Preto, Brazil
Liangxiang Hospital
🇨🇳Beijing, Beijing, China
Santa Casa de Misericórdia de Votuporanga
🇧🇷Votuporanga, Brazil
The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical University
🇨🇳Guangzhou, Guangdong, China
Jixi People's Hospital
🇨🇳Jixi, Heilongjiang, China
Tieli People's Hospital
🇨🇳Yichun, Heilongjiang, China
Luoyang Central's Hospital Affiliated to Zhengzhou University
🇨🇳Luoyang, Henan, China
Suiping Renan Hospital
🇨🇳Zhumadian, Henan, China
Dancheng County People's Hospital
🇨🇳Zhoukou, Henan, China
Tonghua Central Hospital
🇨🇳Tonghua, Jilin, China
Jianshi County People's Hospital
🇨🇳Enshi, Hubei, China
Affiliated Zhongshan Hospital of Dalian University
🇨🇳Dalian, Liaoning, China
Zhengzhou No.7 People's Hospital
🇨🇳Henan, China
Ninghai People's Hospital
🇨🇳Ningbo, Zhejiang, China
Fayoum General Hospital
🇪🇬Fayoum, Egypt
Beijing Anzhen Hospital
🇨🇳Beijing, China
Alexandria University Hospital
🇪🇬Alexandria, Egypt
Assuit General Hospital
🇪🇬Assuit, Egypt
Kasr El Einy Hospital (Cairo University)
🇪🇬Cairo, Egypt
Benha University Cardiology Department
🇪🇬Banha, Egypt
Specialized Medical Hospital - Mansoura
🇪🇬El Mansura, Egypt
Suez Canal University Hospital
🇪🇬Ismailia, Egypt
Hawassa University Referral Hospital
🇪🇹Hawassa, Snnpr, Ethiopia
Govind Ballabh Pant Hospital (GIPMER)
🇮🇳New Delhi, Delhi, India
College of Health Sciences, Addis Ababa University, Black Lion Hospital
🇪🇹Addis Ababa, Ethiopia
Jimma University Hospital
🇪🇹Jimma, Ethiopia
Mekelle University
🇪🇹Mek'ele, Ethiopia
Sri Jayadev Institute of Cardiovascular Sciences and Research
🇮🇳Bangalore, Karnataka, India
Kenyatta National Hospital / University Of Nairobi
🇰🇪Nairobi, Kenya
Hospital Bernardette
🇲🇽Guadalajara, Jalisco, Mexico
Instituto de Investigación del Hospital Cardiológica Aguascalientes
🇲🇽Aguascalientes, Mexico
Centro de Estudios Clínicos de Querétaro S.C.
🇲🇽Queretaro, Querétaro, Mexico
Hospital General Dr. Jorge Soberon Acevedo.Secretaria de Salud del Estado de Guerrero
🇲🇽Guerrero, Mexico
Maputo Central Hospital
🇲🇿Maputo, Mozambique
Instituto Nacional de Cardiología Ignacio Chavez
🇲🇽México, Mexico
Instituto Nacional de Saude & Universidade Eduardo Mondlane
🇲🇿Maputo, Mozambique
Chitwan Medical College
🇳🇵Bharatpur, Nepal
College of Medical Sciences
🇳🇵Bharatpur, Nepal
Gautam Buddha Community Heart Hospital
🇳🇵Butwal, Nepal
Nobel medical college and teaching hospital pvt ltd
🇳🇵Biratnagar, Nepal
Sahid Gangalal Heart Center
🇳🇵Kathmandu, Nepal
Bheri Zonal Hospital
🇳🇵Nepalgunj, Nepal
Federal Medical Center
🇳🇬Abeokuta, Nigeria
University of Nigeria Teaching Hospital
🇳🇬Enugu, Nigeria
College of Medicine, University of Ibadan
🇳🇬Ibadan, Nigeria
Jos University Teaching Hospital
🇳🇬Jos, Nigeria
Aminu Kano University Teaching Hospital
🇳🇬Kano, Nigeria
Department of Medicine, Lagos University Teaching Hospital
🇳🇬Lagos, Nigeria
Ladoke Akintola University of Technology Teaching Hospital
🇳🇬Ogbomoso, Nigeria
Punjab Institute of Cardiology
🇵🇰Lahore, Punjab, Pakistan
Department of Medicine, Delta State University Teaching Hospital
🇳🇬Oghara, Nigeria
Nishtar Hospital Multan
🇵🇰Multan, Pakistan
Isra University Hospital
🇵🇰Hyderabad, Pakistan
Hospital Barrio Obrero
🇵🇾Asunción, Paraguay
Hospital Regional de Ciudad Del Este
🇵🇾Ciudad del Este, Paraguay
Rawalpindi Institute of Cardiology
🇵🇰Rawalpindi, Pakistan
Lady Reading Hospital
🇵🇰Peshawar, Pakistan
Philippine General Hospital
🇵🇭Manila, Philippines
Clinical Hospital
🇵🇾San Lorenzo, Paraguay
Palawan Medical City
🇵🇭Puerto Princesa City, Palawan, Philippines
Philippine Heart Center
🇵🇭Quezon City, Philippines
Quirino Memorial Medical Center
🇵🇭Quezon City, Philippines
Nelson Mandela Academic Hospital
🇿🇦Mthatha, Eastern Cape, South Africa
Charlotte Maxeke Academic Hospital
🇿🇦Johannesburg, Parktown, South Africa
Sefako Makgatho Health Sciences University
🇿🇦Ga-Rankuwa,, Pretoria, South Africa
Cardiology Research Universitas private hospital
🇿🇦Bloemfontein, South Africa
University of Limpopo
🇿🇦Polokwane, South Africa
University of Cape Town
🇿🇦Cape Town, South Africa
Chris Hani Baragwanath Hospital
🇿🇦Soweto, South Africa
Port Elizabeth Hospital Complex
🇿🇦Port Elizabeth, South Africa
Alobeid Teaching Hospital
🇸🇩El Obeid, Sudan
Atbara Teaching Hospital
🇸🇩Atbara, Sudan
Ahmed Gasim Hospital
🇸🇩Khartoum, Sudan
Sudan Heart Center
🇸🇩Khartoum, Sudan
Ahmed Gasim Pediatric Hospital
🇸🇩Khartoum, Sudan
Medani Heart Centre
🇸🇩Wad Medani, Sudan
Muhimbili University of Health and Allied Sciences
🇹🇿Dar es Salaam, Tanzania
University Teaching Hospital (UTH)
🇿🇲Lusaka, Zambia
Mbeya Zonal Referral Hospital
🇹🇿Mbeya, Tanzania
Livingstone Central Hospital
🇿🇲Livingstone, Zambia
Harare Hospital
🇿🇼Harare, Zimbabwe
Mpilo Hospital, National University Science & Technology
🇿🇼Bulawayo, Zimbabwe
Parirenyatwa Hospital
🇿🇼Harare, Zimbabwe
Instituto de Cardiologia do Rio Grande do Sul
🇧🇷Porto Alegre, Brazil
Ahmadu Bello University Teaching Hospital
🇳🇬Kaduna, Nigeria