Can Very Low Dose Rivaroxaban in Addition to Dual Antiplatelet Therapy (DAPT) Improve Thrombotic Status in Acute Coronray Syndrome (ACS) ACS

NCT ID: NCT03775746

Last Updated: 2020-02-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-08
• Study Completion Date: 2021-12-31

Brief Summary

A prospective, randomised, open label study of 3 clinically licensed treatments for ACS to assess the effects of these treatments on blood tests of endogenous fibrinolysis. 50 patients will be randomised to each of the 3 treatment arms in 1:1:1 ratio. Patients will receive the randomised treatment for 1 month after their index admission with ACS.

Detailed Description

Heart attacks are caused by a blood clot occurring in a blood vessel (artery) which supplies blood to the heart. Such a clot can build up and block the blood flow, depriving part of the heart muscle of oxygen and blood, causing transient or permanent damage to the heart muscle.

The standard treatment for a heart attack is two blood thinning medications combined, every day, to reduce the risk of further blood clots forming and to prevent another heart attack. The highest risk of another heart attack is in the next 30 days after the first heart attack.

However, despite two blood thinners combined, some patients still go on to have another clot (heart attack or stroke or death) and this can be life threatening. Earlier research has shown that through a blood test, it is possible to identify patients who remain at increased risk of further clots and who may benefit from further blood thinners to reduce the risk of further heart attack, stroke and death in the next 30 days.

The aim of this study is to test which of 3 blood thinning treatment options (all already in widespread clinical use) is best for patients to reduce further blood clots, in particular the addition of low dose rivaroxaban.

Conditions

Acute Coronary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Clopidogrel with Rivaroxaban

Clopidogrel 75mg o.d. and Rivaroxaban 2.5mg b.i.d.

Group Type: EXPERIMENTAL

Clopidogrel 75Mg Tablet

Intervention Type: DRUG

Prevention of atherothrombotic events in percutaneous coronary intervention (adjunct with aspirin) in patients not already on clopidogrel

Rivaroxaban 2.5Mg Tablet

Intervention Type: DRUG

Prophylaxis of atherothrombotic events following an acute coronary syndrome with elevated cardiac biomarkers (in combination with aspirin alone or aspirin and clopidogrel)

Clopidogrel

Clopidogrel 75mg o.d.

Group Type: ACTIVE_COMPARATOR

Clopidogrel 75Mg Tablet

Intervention Type: DRUG

Prevention of atherothrombotic events in percutaneous coronary intervention (adjunct with aspirin) in patients not already on clopidogrel

Ticagrelor

Ticagrelor 90mg b.i.d.

Group Type: ACTIVE_COMPARATOR

Ticagrelor 90Mg Tablet

Intervention Type: DRUG

Prevention of atherothrombotic events in patients with acute coronary syndrome \[in combination with aspirin\]

Interventions

Clopidogrel 75Mg Tablet

Prevention of atherothrombotic events in percutaneous coronary intervention (adjunct with aspirin) in patients not already on clopidogrel

Intervention Type: DRUG

Rivaroxaban 2.5Mg Tablet

Prophylaxis of atherothrombotic events following an acute coronary syndrome with elevated cardiac biomarkers (in combination with aspirin alone or aspirin and clopidogrel)

Intervention Type: DRUG

Ticagrelor 90Mg Tablet

Prevention of atherothrombotic events in patients with acute coronary syndrome \[in combination with aspirin\]

Intervention Type: DRUG

Other Intervention Names

EU/1/08/465/001; EU/1/08/472/025-035; EU/1/08/472/041; EU/1/08/472/046-047; EU/1/10/655/007-011

Eligibility Criteria

Inclusion Criteria

1. Male and female patients aged 18 years or over

2. Have a diagnosis of acute coronary syndrome requiring treatment with dual antiplatelet therapy

3. Be willing and able to understand the Participant Information Sheet and provide informed consent

4. Agree to comply with the drawing of blood samples for the assessments

Exclusion Criteria

1. Male and female participants aged < 18 years of age.

2. Patient unwilling or unable to give informed consent

3. Patients who might be pregnant or are breast-feeding

4. Active clinically significant bleeding

5. Patient who, in the opinion of the investigator, has condition considered to be a significant risk for major bleeding (such as current or recent gastrointestinal ulceration, presence of malignant neoplasm at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities)

6. Hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C

7. Patient with any contraindications to use of antiplatelet agents or anticoagulants

8. Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of Summary of Product Characteristics (SmPC) of Rivaroxaban

9. Concomitant treatment with any other anticoagulants e.g. unfractionated heparin (UFH), low molecular weight heparins (enoxaparin, dalteparin, etc.), heparin derivatives (fondaparinux, etc.), oral anticoagulants (warfarin, dabigatran etexilate, apixaban etc.) except under specific circumstances of switching anticoagulant therapy or when UFH is given at doses necessary to maintain an open central venous or arterial catheter

10. Concomitant treatment of ACS with antiplatelet therapy in patients with a prior stroke or a transient ischaemic attack (TIA)

11. Patient with ongoing active alcohol or substance abuse or demonstrates signs or clinical features of active substance abuse.

12. Patient with any major bleeding diathesis or blood dyscrasia at baseline (platelets<70 x 109/l, Hb<80 g/l, INR>1.4, APTT> x 2UNL, leucocyte count< 3.5x 109/l, neutrophil count<1x 109/l)

13. Patient currently enrolled in an investigational drug trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Hertfordshire

OTHER

Sponsor Role: collaborator

East and North Hertfordshire NHS Trust

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

East and North Hertfordshire NHS Trust

Stevenage, Hertfordshire, United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Diana A Gorog, MD, PhD, FRCP

Role: CONTACT

d.gorog@nhs.net

01438 284 753

Ying X Gue, MBChB, MRCP

Role: CONTACT

y.gue@nhs.net

01438 284 753

Facility Contacts

Diana A Gorog

Role: primary

d.gorog@nhs.net

+44(0)1707 247512

Ying Gue

Role: backup

y.gue@nhs.net

+44(0)1438 284753

References

Gue YX, Kanji R, Wellsted DM, Srinivasan M, Wyatt S, Gorog DA. Rationale and design of "Can Very Low Dose Rivaroxaban (VLDR) in addition to dual antiplatelet therapy improve thrombotic status in acute coronary syndrome (VaLiDate-R)" study : A randomised trial modulating endogenous fibrinolysis in patients with acute coronary syndrome. J Thromb Thrombolysis. 2020 Feb;49(2):192-198. doi: 10.1007/s11239-019-02014-5.

Reference Type: DERIVED

PMID: 31872349 (View on PubMed)

Other Identifiers

RD2018-41

Identifier Type: -

Identifier Source: org_study_id