Treatment of Cardiovascular Disease With Low Dose Rivaroxaban in Advanced Chronic Kidney Disease

Cardiovascular Disease Clinical Trial

— TRACK  

Official title:

Treatment of Cardiovascular Disease With Low Dose Rivaroxaban in Advanced Chronic Kidney Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03969953
• Other study ID #: 0040139
• Status: Recruiting
• Phase: Phase 3
• Start date: December 14, 2020
• Est. completion date: December 31, 2027

Study information

• Verified date: November 2023
• Source: The George Institute
• Contact: Sunil Badve
• Phone: +61 2 8052 4636
• Email: sbadve[@]georgeinstitute.org.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The TRACK trial is an investigator-initiated, multicentre, prospective, randomised, quadruple-blind (participant, healthcare provider, data collector, outcomes assessor), placebo-controlled trial. TRACK is a global trial and will be conducted in renal units that provide comprehensive CKD care. Approximately 2000 participants will be recruited.

The TRACK trial will assess a strategy of administering low dose rivaroxaban to reduce the risk of major adverse cardiac event (MACE) in people with Chronic Kidney Disease (CKD) stages 4 or 5 or dialysis-dependent kidney failure, and elevated cardiovascular (CV) risk (marked by a history of CAD or PAD, or non-haemorrhagic non-lacunar stroke OR diabetes mellitus OR age ≥65 years).

Description:

Background and Rationale Chronic Kidney Disease (CKD) is a major international health burden. Despite the unacceptably high burden of cardiovascular disease (CVD) and associated mortality, trial-data on the management of CVD in people with advanced stages of CKD and dialysis-dependent kidney failure are sparse. Risk of bleeding in CKD and dialysis-dependent kidney failure is increased when compared to the general population. Anticoagulant agents, such as rivaroxaban, are a core intervention in the prevention of CVD in the general population. Nevertheless, to mitigate trial risks, 90% of the trials evaluating this form of intervention exclude these patient populations.

The TRACK trial will evaluate the effect of low dose rivaroxaban in patients with CKD dialysis-dependent kidney failure. Other trials have demonstrated that rivaroxaban reduces the risk of major cardio-vascular outcomes in high risk patients, and the limited data showed that CKD status did not significantly affect this result.

Hypothesis Compared to placebo, low dose rivaroxaban reduces the risk of major adverse cardiac event (MACE) in people with CKD stages 4 or 5 or dialysis-dependent kidney failure, and elevated cardiovascular (CV) risk (marked by a history of CAD or PAD, or non-haemorrhagic non-lacunar stroke OR diabetes mellitus OR age ≥65 years).

Objectives The primary objective is to determine whether low dose rivaroxaban, compared to placebo, significantly reduces the risk of a composite outcome of;

• CV death,

• non-fatal myocardial infarction,

• stroke, or

• peripheral artery disease (PAD) events

in people with CKD stages 4 or 5 or dialysis-dependent kidney failure, and an elevated CV risk (marked by a history of CAD or PAD, or non-haemorrhagic non-lacunar stroke OR diabetes mellitus OR age ≥65 years).

A full list of secondary objectives are detailed in the protocol, and include identifying risk reduction in the treatment group, and whether this treatment is cost effective.

Methodology The TRACK trial is an investigator-initiated, multicentre, prospective, randomised, quadruple-blind (participant, healthcare provider, data collector, outcomes assessor), placebo-controlled trial. The trial will test for the superiority of the trial intervention using a 1:1 allocation to parallel trial groups, on the basis of a pre-specified number of primary outcomes events.

This is a global trial and will be conducted in renal units that provide comprehensive CKD care. Approximately 2,000 participants will be recruited.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: December 31, 2027
• Est. primary completion date: June 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• People able to provide informed consent who meet all of the following inclusion criteria:

1. Age =18 years,

2. Kidney Failure on haemodialysis or peritoneal dialysis, or CKD stage 4 or 5 (eGFR =29 mL/min/1.73 m2) not receiving renal replacement therapy,

3. Elevated cardiovascular risk, defined by at least one of the following:

1. History of Coronary Artery Disease (CAD) or PAD or non-haemorrhagic non-lacunar stroke, or

2. Diabetes mellitus, or

3. Age =65 years.

Exclusion Criteria:

• Potential participants must have none of the following exclusion criteria at the time of study enrolment:

1. Mechanical/prosthetic heart valve (does not include bioprosthetic valves that do not require therapeutic anticoagulation),

2. Indication for, or contraindication to, anticoagulant therapy,

3. High bleeding risk including any coagulopathy,

4. Lesion or condition considered to be a significant risk of major bleeding,

5. Major bleeding episode in the 30 days prior to study enrolment, or any active and clinically significant bleeding,

6. Current treatment with P2Y12 inhibitors/adenosine diphosphate (ADP) receptor inhibitors (clopidogrel, prasugrel, ticagrelor, cangrelor) or phosphodiesterase inhibitors (dipyridamole), where the treating physician or patient does not wish to stop these medications,

7. Concurrent treatment with strong inhibitors of combined CYP3A4 and P-glycoprotein; or strong inducers of CYP3A4,

8. Any stroke within 1 month prior to enrolment,

9. Any previous history of a haemorrhagic or lacunar stroke,

10. Severe heart failure with known ejection fraction <30% or New York Heart Association class III or IV symptoms,

11. History of hypersensitivity or known contraindication to rivaroxaban,

12. Uncontrolled hypertension (systolic BP =180 mm Hg or diastolic BP =110 mm Hg), at the time of screening

13. Haemoglobin <90 g/L, or platelet count <100 x 109/L,

14. Significant liver disease (defined as Child-Pugh Class B or C) or Alanine Aminotransferase (ALT) >3 times upper normal limit,

15. Kidney transplant recipients with a functioning allograft, or scheduled for living-donor kidney transplant surgery,

16. All countries except Europe: Pregnancy or intention to become pregnant or breast-feeding; Europe only: Women who are not in a postmenopausal state, where postmenopausal is defined as no menses for 12 months without alternative medical causes,

17. Inability to understand or comply with the requirements of the study.

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Chronic Kidney Diseases
• Kidney Diseases
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Drug:
• Rivaroxaban 2.5 Mg Oral Tablet
Rivaroxaban is an orally administered selective direct factor Xa inhibitor.

Other:
• Placebo
Rivaroxaban matched placebo

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Armadale Hospital	Armadale	Western Australia
Australia	Bendigo Health	Bendigo	Victoria
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Canberra Hospital	Garran	Australian Capital Territory
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	St George Hospital	Kogarah	New South Wales
Australia	Logan Hospital	Meadowbrook	Queensland
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Sunshine Hospital	St Albans	Victoria
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	Wollongong Hospital	Wollongong	New South Wales
Canada	Research St. Joseph's - Hamilton	Hamilton
Canada	Ottawa Hospital Research Institute	Ottawa
France	Hôpital de Mercy, (CH Metz-Thionville)	Ars-Laquenexy
France	Hôpital Ambroise Paré, (AP-HP)	Boulogne-Billancourt
France	CH Boulogne-sur-Mer, (CH Boulogne-sur-Mer)	Boulogne-sur-Mer
France	Hôpital de la Cavale Blanche, (CHU Brest)	Brest
France	AURAL Colmar, (AURAL Colmar)	Colmar
France	AURAL Haguenau, (AURAL Haguenau)	Haguenau
France	CH Haguenau, (CH Haguenau)	Haguenau
France	ALURAD Buisson, (ALURAD Buisson)	Limoges
France	CHU Dupuytren, (CHU Dupuytren)	Limoges
France	Hôpital Edouard Herriot, (CHU Lyon)	Lyon
France	Hôpital de la Conception, (AP-HM)	Marseille
France	AURAL Mulhouse, (AURAL Mulhouse)	Mulhouse
France	CH Mulhouse, (CH Mulhouse)	Mulhouse
France	Centre Hospitalier Régional Universitaire de Nancy	Nancy	Meurthe-et-Moselle
France	Hôpital Pasteur, (CHU Nice)	Nice
France	Hôpital Lyon Sud, (CHU Lyon)	Pierre-Bénite
France	Hôpital de la Maison Blanche, (CHU Reims)	Reims
France	AURAL Strasbourg, (AURAL Strasbourg)	Strasbourg
France	Hôpital Bretonneau, (CHRU Tours)	Tours
France	Hôpitaux de Brbaois, (ALTIR)	Vandœuvre-lès-Nancy
India	All India Institute of Medical Sciences, Bathinda	Bathinda	Punjab
India	Postgraduate Institute of Medical Education and Research, Chandigarh	Chandigarh
India	Aysha Hospital	Chennai	Tamil Nadu
India	KG Hospital, K.Govindaswamy Naidu Medical Trust	Coimbatore
India	Noble Annex Hospital	Hadapsar	Pune Maharashtra
India	Citizens Hospital	Hyderabad	Telangana
India	Nizam's Institute of Medical Sciences, Hyderabad	Hyderabad	Telangana
India	Osmania General Hospital	Hyderabad	Telangana
India	VS Hospital	Kilpauk
India	Institute of Post-Graduate Medical Education and Research	Kolkata
India	Aykai Super Speciality Hospital, Ludhiana	Ludhiana	Punjab
India	Muljibhai Patel Urological Hospital	Nadiad	Gujarat
India	Government Hospital	Nandyal
India	Government Hospital	Proddatur
India	All India Institute Of Medical Sciences, Raipur	Raipur	Chhattisgarh
India	Sooriya Hospital	Saligramam
India	Kasturba Medical College and Hospital, Manipal	Udupi	Karnataka
India	L & T Prayas Medical Centre	Virugambakkam
Malaysia	Hospital Sultanah Bahiyah	Alor Setar	Kedah
Malaysia	Hospital Raja Permaisuri Bainun, Ipoh	Ipoh	Perak
Malaysia	Hospital Kajang	Kajang	Selangor
Malaysia	Hospital Raja Perempuan Zainab II	Kota Bharu	Kelantan
Malaysia	Hospital Queen Elizabeth, Kota Kinabalu	Kota Kinabalu	Sabah
Malaysia	Hospital Canselor Tuanku Muhriz	Kuala Lumpur	Wilayah Persekutuan
Malaysia	University of Malaya Medical Centre	Kuala Lumpur	Wilayah Persekutuan
Malaysia	Hospital Seberang Jaya	Seberang Jaya	Penang
Malaysia	Hospital Tuanku Ja'afar, Seremban	Seremban	Negeri Sembilan
Saudi Arabia	Hemodialysis Care Project North Centre	Al-Yasmin	Riyadh
Saudi Arabia	Hemodialysis King Abdullah Centre	Al-Yasmin	Riyadh
Saudi Arabia	ialysis Centre - King Abdul Aziz Medical City (KAMC)	Ar-Rimayah	Riyadh
Saudi Arabia	Hemodialysis Care Project South Centre	Riyad	Riyadh
Saudi Arabia	King Abdullah International Medical Research Center	Riyadh
Singapore	Khoo Teck Puat Hospital	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
Taiwan	Kaohsiung Chang-Gung Memorial Hospital	Kaohsiung
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Chung-Shan Medical University Hospital	Taichung
Taiwan	Taipei Tzu Chi Hospital	Taipei
Taiwan	Wan fang Hospital	Taipei
Taiwan	Fu-Jen Catholic University Hospital	Taishan	New Taipei City
Taiwan	Chang Gung Memorial Hospital, Linkou Medical Center	Taoyuan
Tunisia	Fattouma Bourguiba Hospital	Monastir
Tunisia	Hedi chaker Hospital	Sfax
Tunisia	Sahloul Hospital	Sousse
Tunisia	Charles Nicolle Hospital	Tunis
Tunisia	La Rabta Hospital	Tunis
Tunisia	Military Hospital	Tunis
Tunisia	Mongi Slim Hospital	Tunis

Sponsors (5)

Lead Sponsor	Collaborator
The George Institute	Bayer, Centre Hospitalier Régional Universitaire de Nancy, George Clinical Pty Ltd, King Abdullah International Medical Research Center

Countries where clinical trial is conducted

Australia,  Canada,  France,  India,  Malaysia,  Saudi Arabia,  Singapore,  Taiwan,  Tunisia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Cost Effectiveness of Intervention - Cost of intervention, & Net benefit in time to MACE event in intervention, when compared to placebo.	To determine whether the intervention, compared to placebo, is cost effective. Where the primary outcome is positive, the cost of providing the intervention will be assessed against the MACE benefit achieved to determine if the treatment meets regulatory guidelines for cost effectiveness. E.g of the Australian Pharmaceutical Benefits Scheme (PBS).	5 years or trial closure
Other	Incidence of Thrombosis of dialysis vascular access	To determine whether the intervention, compared to placebo, changes the risk of thrombosis of dialysis vascular access among participants with an arteriovenous fistula/graft.	5 years or trial closure
Primary	Risk of Major Adverse Cardiac Event (MACE)	To determine whether the intervention, compared to placebo, changes the risk of a composite outcome of; CV death,; non-fatal myocardial infarction,; stroke, or; peripheral artery disease (PAD) events	5 years or trial closure
Secondary	Composite outcome of cardiovascular death, non-fatal myocardial infarction, or stroke.	To determine whether the intervention, compared to placebo, changes the risk of a composite outcome of cardiovascular death, non-fatal myocardial infarction, or stroke.	5 years or trial closure
Secondary	Composite outcome of all-cause death, non-fatal myocardial infarction, stroke, or PAD events.	To determine whether the intervention, compared to placebo, changes the risk of a composite of all-cause death, non-fatal myocardial infarction, stroke, or PAD events.	5 years or trial closure
Secondary	Composite outcome of all-cause death, non-fatal myocardial infarction, or stroke.	To determine whether the intervention, compared to placebo, changes the risk of a composite of all-cause death, non-fatal myocardial infarction, or stroke.	5 years or trial closure
Secondary	Incidence of Cardiovascular Death	To determine whether the intervention, compared to placebo, changes the risk of Cardiovascular Death	5 years or trial closure
Secondary	Incidence of Non-Fatal Myocardial Infarction	To determine whether the intervention, compared to placebo, changes the risk of Non-Fatal Myocardial Infarction	5 years or trial closure
Secondary	Incidence of Stroke	To determine whether the intervention, compared to placebo, changes the risk of Stroke	5 years or trial closure
Secondary	Incidence of PAD Events	To determine whether the intervention, compared to placebo, changes the risk of PAD events	5 years or trial closure
Secondary	Net Clinical Benefit - incidence of MACE & Bleeding	To determine whether the intervention, compared to placebo, changes the risk of a composite outcome of cardiovascular death, non-fatal myocardial infarction, stroke, PAD events, fatal bleeding, or symptomatic bleeding into a critical organ.	5 years or trial closure
Secondary	Incidence of Venous Thromboembolism	To determine whether the intervention, compared to placebo, changes the risk of Venous Thromboembolism	5 years or trial closure

External Links

•   Trial Website