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

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.

Study Overview

• Status: Unknown
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Drug: Clopidogrel 75Mg Tablet; Drug: Rivaroxaban 2.5Mg Tablet; Drug: Ticagrelor 90Mg Tablet

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.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Diana A Gorog, MD, PhD, FRCP; Phone Number: 01438 284 753; Email: d.gorog@nhs.net
• Study Contact Backup: Name: Ying X Gue, MBChB, MRCP; Phone Number: 01438 284 753; Email: y.gue@nhs.net

Study Locations

• United Kingdom
  • Hertfordshire
    • Stevenage, Hertfordshire, United Kingdom, SG1 4AB
      • Recruiting
      • East and North Hertfordshire NHS Trust
      • Contact: Diana A Gorog; Phone Number: +44(0)1707 247512; Email: d.gorog@nhs.net
      • Contact: Ying Gue; Phone Number: +44(0)1438 284753; Email: y.gue@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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
5. Not meet any of the exclusion criteria below

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clopidogrel with Rivaroxaban; Clopidogrel 75mg o.d. and Rivaroxaban 2.5mg b.i.d.	Drug: Clopidogrel 75Mg Tablet; Prevention of atherothrombotic events in percutaneous coronary intervention (adjunct with aspirin) in patients not already on clopidogrel; Other Names: EU/1/08/465/001; 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); Other Names: EU/1/08/472/025-035; EU/1/08/472/041; EU/1/08/472/046-047
Active Comparator: Clopidogrel; Clopidogrel 75mg o.d.	Drug: Clopidogrel 75Mg Tablet; Prevention of atherothrombotic events in percutaneous coronary intervention (adjunct with aspirin) in patients not already on clopidogrel; Other Names: EU/1/08/465/001
Active Comparator: Ticagrelor; Ticagrelor 90mg b.i.d.	Drug: Ticagrelor 90Mg Tablet; Prevention of atherothrombotic events in patients with acute coronary syndrome [in combination with aspirin]; Other Names: EU/1/10/655/007-011

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in Lysis Time (LT) in the three treatment groups assessed using the GTT from admission to follow-up at 30 days	To investigate, in patients with recent acute coronary syndrome and who have impaired endogenous fibrinolysis, whether the addition of low dose rivaroxaban to DAPT can improve endogenous thrombotic and fibrinolytic status	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of further angioplasty	Clinical events including re-intervention	6 months
Frequency of further heart attack, stroke or death	Incidence of further major adverse cardiac events	6 months

Collaborators and Investigators

• Sponsor: East and North Hertfordshire NHS Trust
• Collaborators: University of Hertfordshire

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2019
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: December 12, 2018
• First Submitted That Met QC Criteria: December 12, 2018
• First Posted (Actual): December 14, 2018

Study Record Updates

• Last Update Posted (Actual): February 12, 2020
• Last Update Submitted That Met QC Criteria: February 11, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Ticagrelor; Clopidogrel; Rivaroxaban
• Other Study ID Numbers: RD2018-41

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No