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AzTrials

Rheumatic Heart DiseasePhase 3INVICTUS-VKANCT02832544

INVestIgation of rheumatiC AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies, Non-Inferiority

A Phase 3 study testing Rivaroxaban (20 mg) and Vitamin K antagonists (VKA) in people with Rheumatic Heart Disease, run by Population Health Research Institute at 139 sites in 25 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Rheumatic Heart Disease
What is being tested?
Rivaroxaban (20 mg) and Vitamin K antagonists (VKA)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4,565 participants
Where
139 sitesin 25 countries
Study dates
22 Aug 2016to 18 Aug 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 19Show fewer
  • 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.

Trial locations and contacts

139 sites in 25 countries.

139 sites in 25 countries

China22 sites

  • Liangxiang Hospital

    Beijing, Beijing Municipality, 102401

  • Beijing Anzhen Hospital

    Beijing, 100029

  • Pi County People's Hospital

    Chengdu, Sichuan, 611730

  • Affiliated Zhongshan Hospital of Dalian University

    Dalian, Liaoning, 116001

  • The First Affiliated Hospital of Dalian Medical University

    Dalian, Liaoning, 116011

  • Jianshi County People's Hospital

    Enshi, Hubei, 445308

  • The First Affiliated Hospital/School of Clinical Medicine of Guangdong Pharmaceutical University

    Guangzhou, Guangdong, 510062

  • Zhongmou County People's Hospital

    Henan, 450000

  • Zhengzhou No.7 People's Hospital

    Henan, 450016

  • Zhengzhou 9th People's Hospital

    Henan, 450053

  • Guangshan County People's Hospital

    Henan

  • Jixi People's Hospital

    Jixi, Heilongjiang, 158100

  • Luoyang Central's Hospital Affiliated to Zhengzhou University

    Luoyang, Henan, 471009

  • Ninghai People's Hospital

    Ningbo, Zhejiang, 315600

  • Suqian Peaple's Hospital of Nanjing Drum-Tower Hospital Group

    Suqian, Jiangsu, 223800

  • Tonghua Central Hospital

    Tonghua, Jilin, 134001

  • Wendeng Central Hospital

    Weihai, Wendeng

  • Tieli People's Hospital

    Yichun, Heilongjiang, 152500

  • Ningxia Peple's Hospital

    Yinchuan, Ningxia, 750021

  • Dancheng County People's Hospital

    Zhoukou, Henan, 477150

  • Suiping Renan Hospital

    Zhumadian, Henan, 463100

  • Anyue County People's Hospital

    Ziyang, Sichuan, 642350

Other trials in China

Egypt14 sites

  • Fayoum General Hospital

    Al Fayyum, 31951

  • Mehallah Rheumatic Heart Center

    Al Mansurah, 31951

  • Specialized Medical Hospital - Mansoura

    Al Mansurah, 35516

  • Alexandria University Hospital

    Alexandria, 21561

  • Assuit General Hospital

    Asyut

  • Benha University Cardiology Department

    Banhā

  • Beni Suef University Hospital

    Banī Suwayf

  • Ain Shams University Hospital

    Cairo, 11566

  • Kasr El Einy Hospital (Cairo University)

    Cairo, 21561

  • Suez Canal University Hospital

    Ismailia, 41522

  • El Minia University Hospital

    Minya, 61519

  • Sohag University, Sohag

    Sohag, 35516

  • Red Crescent Hospital

    Tanta, 31951

  • Zagazig University Hospital

    Zagazig, 44519

Other trials in Egypt

Brazil12 sites

  • Cardresearch - Cardiologia Assistencial e de Pesquisa

    Belo Horizonte, Minas Gerais, 30150-240

  • Clínica Procardio Ltda.

    Blumenau, Santa Catarina, 89010-500

  • Instituto de Pesquisa Clínica de Campinas

    Campinas, 13060-080

  • LOEMA - Instituto de Pesquisa Clínica & Consultores Ltda

    Campinas, São Paulo

  • Via Médica Centro Clínico Barroso e Sebba Ltda

    Goiânia, 74223130

  • Instituto de Cardiologia do Rio Grande do Sul

    Porto Alegre, 90620001

  • Fundação Faculdade de Medicina de São José do Rio Preto

    São José do Rio Preto, 1509000

  • Instituto do Coração - HCFMUSP

    São Paulo, 05403-000

  • Instituto Dante Pazzanese de Cardiologia

    São Paulo, 4012909

  • Nucleo de Estudios Clinicos - Universidade Federal do Triângulo Mineiro

    Uberaba, Minas Gerais

  • Eurolatino Pesquisas Médicas Ltda

    Uberlândia, Minas Gerais, 38411-186

  • Santa Casa de Misericórdia de Votuporanga

    Votuporanga, 15500-003

Other trials in Brazil

Nepal9 sites

  • College of Medical Sciences

    Bharatpur, 44207

  • Chitwan Medical College

    Bharatpur

  • Nobel medical college and teaching hospital pvt ltd

    Biratnagar, 56613

  • Gautam Buddha Community Heart Hospital

    Butwal, 32907

  • BP Koirala Institute of Health Sciences

    Dharān, 56700

  • Manmohan Cardiothoracic Vascular and Trasplant Center, IOM, TU

    Kathmandu, 44600

  • Sahid Gangalal Heart Center

    Kathmandu, 44600

  • Bheri Zonal Hospital

    Nepalgunj, 21900

  • Manipal College of Medical Sciences

    Pokhara, 33700

Other trials in Nepal

Nigeria9 sites

  • Federal Medical Center

    Abeokuta

  • University of Nigeria Teaching Hospital

    Enugu, 400201

  • College of Medicine, University of Ibadan

    Ibadan, 200212

  • Jos University Teaching Hospital

    Jos, 930001

  • Ahmadu Bello University Teaching Hospital

    Kaduna, 810001

  • Aminu Kano University Teaching Hospital

    Kano, 700223

  • Department of Medicine, Lagos University Teaching Hospital

    Lagos, 12003

  • Ladoke Akintola University of Technology Teaching Hospital

    Ogbomoso, 4007

  • Department of Medicine, Delta State University Teaching Hospital

    Oghara

Other trials in Nigeria

South Africa8 sites

  • Cardiology Research Universitas private hospital

    Bloemfontein, 9301

  • University of Cape Town

    Cape Town, 7925

  • Sefako Makgatho Health Sciences University

    Ga-Rankuwa, Pretoria, 0204

  • Charlotte Maxeke Academic Hospital

    Johannesburg, Parktown, 2193

  • Nelson Mandela Academic Hospital

    Mthatha, Eastern Cape, 5099

  • University of Limpopo

    Polokwane, 700

  • Port Elizabeth Hospital Complex

    Port Elizabeth, 6001

  • Chris Hani Baragwanath Hospital

    Soweto, 2013

Other trials in South Africa

Sudan8 sites

  • Alobeid Teaching Hospital

    Al-Ubayyid

  • Atbara Teaching Hospital

    Atbara

  • Ahmed Gasim Hospital

    Khartoum, 1111

  • Alshaab Teaching Hospital

    Khartoum, 1111

  • Ahmed Gasim Pediatric Hospital

    Khartoum

  • Sudan Heart Center

    Khartoum

  • Digna Prince Hospital

    Port Sudan

  • Medani Heart Centre

    Wad Medani

Other trials in Sudan

India7 sites

  • Sri Jayadev Institute of Cardiovascular Sciences and Research

    Bangalore, Karnataka, 560069

  • SMS Medical College

    Jaipur, Rajasthan, 302004

  • King George's Medical College

    Lucknow, Uttar Pradesh, 226003

  • Sanjay Gandhi Post Graduate Institute of Medical Sciences

    Lucknow, Uttar Pradesh, 226014

  • Dr. Ram Manohar Lohia Hospital @ PGIMER

    New Delhi, National Capital Territory of Delhi, 110001

  • Govind Ballabh Pant Hospital (GIPMER)

    New Delhi, National Capital Territory of Delhi, 110002

  • All India Institute of Medical Sciences

    New Delhi, National Capital Territory of Delhi, 110029

Other trials in India

Mexico7 sites

  • Instituto de Investigación del Hospital Cardiológica Aguascalientes

    Aguascalientes, 20230

  • Centro para el Desarrollo de la Medicina y Asistencia Especializada S.C.

    Culiacán, Sinaloa, 80230

  • Hospital Bernardette

    Guadalajara, Jalisco, 44200

  • Hospital General Dr. Jorge Soberon Acevedo.Secretaria de Salud del Estado de Guerrero

    Guerrero, 40000

  • Hospital Angeles León

    León, Guanajuato, 37150

  • Instituto Nacional de Cardiología Ignacio Chavez

    México, 14080

  • Centro de Estudios Clínicos de Querétaro S.C.

    Querétaro City, Querétaro, 76000

Other trials in Mexico

Pakistan5 sites

  • Isra University Hospital

    Hyderābād, 31300

  • Punjab Institute of Cardiology

    Lahore, Punjab Province, 54000

  • Nishtar Hospital Multan

    Multan, 60000

  • Lady Reading Hospital

    Peshawar, PK 2500

  • Rawalpindi Institute of Cardiology

    Rawalpindi, 46000

Other trials in Pakistan

Paraguay5 sites

  • Instituto Nacional de Cardiología

    Asunción, 1725

  • Hospital Barrio Obrero

    Asunción, 2279

  • Hospital Regional de Ciudad Del Este

    Ciudad del Este, 7000

  • Hospital Nacional Itaugua

    Itauguá, 2740

  • Clinical Hospital

    San Lorenzo, 1863

Other trials in Paraguay

Cameroon4 sites

  • Clinique Coeur Et Vie

    Douala, 7562

  • Douala General Hospital

    Douala

  • St. Elizabeth Catholic General Hospital, Cardiac Centre

    Kumbo

  • Hopital Central Yaounde

    Yaoundé

Other trials in Cameroon

Ethiopia4 sites

  • College of Health Sciences, Addis Ababa University, Black Lion Hospital

    Addis Ababa, 1176

  • Hawassa University Referral Hospital

    Awasa, Snnpr

  • Jimma University Hospital

    Jimma

  • Mekelle University

    Mek'ele, 1871

Other trials in Ethiopia

Philippines4 sites

  • Philippine General Hospital

    Manila, 1000

  • Palawan Medical City

    Puerto Princesa City, Palawan, 5300

  • Philippine Heart Center

    Quezon City, 1100

  • Quirino Memorial Medical Center

    Quezon City, 1109

Other trials in Philippines

Kenya3 sites

  • Moi Teaching and Referral Hospital

    Eldoret, 30100

  • Karen Hospital

    Nairobi, 00200

  • Kenyatta National Hospital / University Of Nairobi

    Nairobi

Other trials in Kenya

Malawi3 sites

  • Queen Elizabeth Central Hospital

    Blantyre, 265

  • Kumuzu Central Hospital

    Lilongwe, 265

  • Mzuzu Central Hospital

    Mzuzu, 265

Other trials in Malawi

Zambia3 sites

  • Livingstone Central Hospital

    Livingstone, 10101

  • University Teaching Hospital (UTH)

    Lusaka

  • Ndola Central Hospital

    Ndola, 10101

Other trials in Zambia

Zimbabwe3 sites

  • Mpilo Hospital, National University Science & Technology

    Bulawayo

  • Harare Hospital

    Harare

  • Parirenyatwa Hospital

    Harare

Other trials in Zimbabwe

Mozambique2 sites

  • Maputo Central Hospital

    Maputo, 1111

  • Instituto Nacional de Saude & Universidade Eduardo Mondlane

    Maputo, CP 264

Other trials in Mozambique

Tanzania2 sites

  • Muhimbili University of Health and Allied Sciences

    Dar es Salaam

  • Mbeya Zonal Referral Hospital

    Mbeya, 419

Other trials in Tanzania

Botswana1 site

  • Princess Marina Hospital

    Gaborone

Other trials in Botswana

Kazakhstan1 site

  • Kazakh National Medical Institute,

    Almaty

Other trials in Kazakhstan

Kyrgyzstan1 site

  • Clinical Hospital of administrative department of President and Government of Kyrgyz Republic

    Bishkek, 720001

Other trials in Kyrgyzstan

Rwanda1 site

  • University of Rwanda, Kigali University Teaching Hospital

    Kigali

Other trials in Rwanda

Uganda1 site

  • Uganda Heart Institute

    Kampala

Other trials in Uganda

About this study

Official title: INVestIgation of rheumatiC AF Treatment Using Vitamin K Antagonists, Rivaroxaban or Aspirin Studies

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.

Read the 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
  4. CHA2DS2-VASc score ≥ 2 OR
  5. Moderate/Severe mitral stenosis with valve area ≤2.0 cm2 OR
  6. Left atrial spontaneous echo contrast OR
  7. Left atrial thrombus
  8. 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)
  1. VKA Arm
  • Any VKA approved for use in the participating country
  • VKA titrated to achieve an INR of 2.0-3.0
Being tested
Rivaroxaban (20 mg), Vitamin K antagonists (VKA)
Keywords
atrial fibrillation, stroke
Medical subject headings
Rheumatic Heart Disease, Atrial Fibrillation, Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Rivaroxaban (20 mg)Drug

    Also called Xarelto

    Rivaroxaban is non-inferior to VKAs for the prevention of stroke or systemic embolism in patients with AF/flutter and RVHD and potentially superior to VKAs.

  • Vitamin K antagonists (VKA)Drug

    Also called Warfarin

Study groups in NCT02832544
Study groupRoleWhat they receive
Rivaroxaban (20 mg)ExperimentalRivaroxaban 20 mg od (n ~ 2250); 15 mg od (once daily) in patients with creatinine clearance (CrCl) 15-49 ml/min
Receives: Drug: Rivaroxaban (20 mg)
Vitamin K antagonists (VKA)Active comparatorAny approved VKA in the participating country (n ~ 2250); VKA titrated to achieve an INR of 2.0-3.0
Receives: Drug: Vitamin K antagonists (VKA)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time from randomization to the first occurrence of vascular death or death of unknown cause, stroke, myocardial infarction or systemic embolism

    Vascular death or death of unknown cause, stroke, myocardial infarction or systemic embolism

    Measured: Approximately 4 years

Secondary outcomes (1)

  1. Time from randomization to the first occurrence of composite of stroke or systemic embolism

    Composite of stroke or systemic embolism

    Measured: Approximately 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jul 2016 (estimated)
  2. Study start22 Aug 2016
  3. Primary completion18 Aug 2022
  4. Study completion18 Aug 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
4,565 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02832544
Sponsor's protocol ID
INVICTUS - VKA
Acronym
INVICTUS-VKA
Status last verified
Jul 2022
First submitted
10 Dec 2015
Last updated
5 Oct 2022
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No: cumulative participant data only

Publications

  • Connolly SJ, Karthikeyan G, Ntsekhe M, Haileamlak A, El Sayed A, El Ghamrawy A, Damasceno A, Avezum A, Dans AML, Gitura B, Hu D, Kamanzi ER, Maklady F, Fana G, Gonzalez-Hermosillo JA, Musuku J, Kazmi K, Zuhlke L, Gondwe L, Ma C, Paniagua M, Ogah OS, Molefe-Baikai OJ, Lwabi P, Chillo P, Sharma SK, Cabral TTJ, Tarhuni WM, Benz A, van Eikels M, Krol A, Pattath D, Balasubramanian K, Rangarajan S, Ramasundarahettige C, Mayosi B, Yusuf S; INVICTUS Investigators. Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation. N Engl J Med. 2022 Sep 15;387(11):978-988. doi: 10.1056/NEJMoa2209051. Epub 2022 Aug 28.

    PubMed 36036525

  • Karthikeyan G, Connolly SJ, Yusuf S. Overestimation of Stroke Risk in Rheumatic Mitral Stenosis and the Implications for Oral Anticoagulation. Circulation. 2020 Nov 3;142(18):1697-1699. doi: 10.1161/CIRCULATIONAHA.120.050347. Epub 2020 Nov 2. No abstract available.

    PubMed 33136507

  • Karthikeyan G, Connolly SJ, Ntsekhe M, Benz A, Rangarajan S, Lewis G, Yun Y, Sharma SK, Maklady F, Elghamrawy AE, Kazmi K, Cabral TTJ, Dayi H, Changsheng M, Gitura BM, Avezum A, Zuhlke L, Lwabi P, Haileamlak A, Ogah O, Chillo P, Paniagua M, ElSayed A, Dans A, Gondwe-Chunda L, Molefe-Baikai OJ, Gonzalez-Hermosillo JA, Hakim J, Damasceno A, Kamanzi ER, Musuku J, Davletov K, Connolly K, Mayosi BM, Yusuf S; INVICTUS Investigators. The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation. Am Heart J. 2020 Jul;225:69-77. doi: 10.1016/j.ahj.2020.03.018. Epub 2020 Mar 25.

    PubMed 32474206

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rivaroxaban (20 mg) and Vitamin K antagonists (VKA) in people with Rheumatic Heart Disease, run by Population Health Research Institute at 139 sites in 25 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 139 sites in China, Egypt, Brazil, Nepal, Nigeria and 20 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time from randomization to the first occurrence of vascular death or death of unknown cause, stroke, myocardial infarction or systemic embolism (time frame: Approximately 4 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02832544, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2022.

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