SHORT RUN AF "Rivaroxaban versus standard of care for patients with excessive atrial ectopy or short atrial runs and high embolism risk"

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

18 Apr 2023 → 28 Aug 2025

Decision date (initial)

2024-10-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS

External identifiers

EU CT number

2024-516374-29-00

EudraCT number

2020-004784-53

ClinicalTrials.gov

NCT05487950

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

evaluate the efficacy and safety of long term anticoagulation with rivaroxaban against standard of care (SOC) in patients with ESVEA and CHA2DS2VASC score ≥3 on the incidence of ischemic stroke
and peripheral embolism after 2 years follow-up and the occurrence of major bleeding events.

Secondary objectives 3

1. Efficacy-related objectives:To compare randomized groups on net clinical benefit, major cardiovascular events, overall survival, cognitive decline. o To compare randomized groups on individual components of composite primary and secondary efficacy endpoints
2. Exploratory objectives: o To describe and compare between randomized groups the incidence of documented atrial fibrillation diagnosed from patient symptoms or systematic 24 hours ECG Holter performed at 1 year and 2-year follow-up. o To evaluate through cerebral MRI the incidence of asymptomatic cerebral damage including silent cerebral ischemia and microbleeds at 2-year followup.
3. Safety-related objectives: o To assess the occurrence of life-threatening or fatal bleeding, clinically relevant non-major bleeding intracranial hemorrhage and minor bleeding

Conditions and MedDRA coding

Patients with excessive supraventricular ectopies or short atrial runs (ESVEA) defined as ≥ 1% premature atrial contractions (PAC) /24 hours or any atrial runs ≥ 20 PACs (but shorter than 30 seconds) on a 24-hour Holter ECG monitoring and CHA2DS2VASC score ≥ 3. Patients with any atrial runs ≥ 20 PACs but shorter than 30 seconds on a 15-21 days Holter ECG monitoring and CHA2DS2VASC score ≥ 3 may also be included in the Short-Run trial.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Patients ≥ 65 years old
2. Diagnosis of excessive supraventricular ectopy activity defined as: i) ≥ 1% PAC / 24 h or any atrial runs ≥ 20 PACs (shorter than 30 seconds) on a 24-hour Holter ECG monitoring (the indication for the Holter will be let at the discretion of the doctor according to international guidelines indication) ii) Or any atrial runs ≥ 20 PACs but shorter than 30 seconds on a 15-21 days Holter ECG monitoring
3. High risk embolism defined by a CHA2DS2VASC score ≥ 3
4. Written consent from patient
5. Patients able to attend consultations and Cerebral MRI at baseline and 24 months at the participating centre.
6. Ability to understand and comply with the study protocol
7. Affiliation of social security regime

Exclusion criteria 32

1. According to the SmPC, any contraindication to Rivaroxaban (particularly patients with ongoing major bleeding, vascular complication, prior haemorrhagic stroke or over recent stroke) or one of its excipients.
2. Inability to perform cerebral MRI
3. Life expectancy <24 months
4. History of major hemorrhage after taking Rivaroxaban
5. Documented atrial fibrillation or any other indication for oral anticoagulation
6. Patients with previous documented AF
7. Valvular congenital heart disease
8. Anticoagulant agents in the month prior to the inclusion visit
9. Acute coronary syndrome, coronary revascularization (percutaneous coronary intervention or coronary artery bypass surgery) or in the past 30 days
10. Requires long-term antiplatelet therapy other than aspirin (i.e., patient requires any platelet aggregation inhibitor in addition to study treatment, in particular, the combination of two platelet aggregation inhibitors)
11. Ongoing need for strong inhibitors of both CYP3A4 and P-glycoprotein (e.g., ketoconazole, itraconazole, ritonavir or clarithromycin)
12. Ongoing need for strong inducers of both CYP3A4 and P-glycoprotein (e.g., rifampin, carbamazepine, phenytoin)
13. Participants considered by the investigator to be unsuitable for the study for any of the following reasons:  Patient refuse the treatment with rivaroxaban or anticipated to have poor compliance on study drug treatment  Unwilling to attend study follow-up visits
14. Cancer or other life threatening conditions
15. Severe, disabling stroke within the previous 6 months, or any stroke within the previous 14 days
16. Conditions associated with an increased risk of bleeding: a. Major surgery within the previous month b. Planned surgery or intervention within the next 3 months c. History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding d. Gastrointestinal hemorrhage within the past year e. Symptomatic or endoscopically documented gastroduodenal ulcer disease in the previous 30 days f. Hemorrhagic disorder or bleeding diathesis g. Need for anticoagulant treatment of disorders other than atrial fibrillation h. Fibrinolytic agents within 48 hours of study entry i. Uncontrolled hypertension (systolic blood pressure greater than 180 mm Hg and/or diastolic blood pressure greater than 100 mm Hg) j. Recent malignancy or radiation therapy (within 6 months) and not expected to survive 3 years
17. Severe renal impairment (estimated creatinine clearance <30 mL/min or less)
18. Active infective endocarditis
19. Active liver disease, including but not limited to, associated or not with coagulopathy and a clinically significant risk of bleeding, including cirrhotic patients with a Child Pugh class B or C score.
20. Persistent ALT, AST, Alk Phos greater than twice the upper limit of the normal range
21. Known active hepatitis C (positive HCV RNA)
22. Known active hepatitis B (HBs antigen +, anti HBc IgM +)
23. Known active hepatitis A
24. Anemia (hemoglobin level less than 110 g/L) or thrombocytopenia (platelet count less than 150 X 109/L)
25. Patients who have received an investigational drug in the past 30 days
26. Patients considered unreliable by the investigator, or having any condition which, in the opinion of the investigator, would not allow safe participation in the study (e.g., drug addiction, alcohol abuse)
27. Patient with cardiac prosthetic devices : Reveal, pace-maker, automatic implantable defibrillator
28. Participation in another interventional clinical trial
29. Patient on AME (state medical aid)
30. Persons under psychiatric care
31. Adults subject to a legal protection measure (guardianship, curatorship and safeguard of justice)
32. Patients deprived of their liberty by a judicial or administrative decision

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The primary efficacy endpoint is the first ischemic stroke or peripheral embolism detected clinically and on systematic cerebral MRIs in a time-to-event analysis.
2. The primary safety outcome is major bleeding at any site in the body according to the criteria of the International Society of Thrombosis and Hemostasis (ISTH)(23-25).

Secondary endpoints 3

1. Efficacy-related endpoints: o A composite of ischemic stroke, peripheral embolism or major bleeding (net clinical benefit); a composite of death from cardiovascular causes, stroke, systemic embolism, myocardial infarction (major cardiovascular events); death from any cause; cognitive decline as assessed by the MMS (26). o Individual components of composite primary and secondary efficacy endpoints
2. Exploratory endpoints: o Incidence of documented atrial fibrillation diagnosed from patient symptoms or systematic 24 hours ECG Holter performed at 1- and 2-year follow-up. o Incidence of asymptomatic MRI-detected cerebral damage including silent cerebral ischemia and microbleeds at 2-year follow up.
3. Safety-related endpoints: o Life-threatening or fatal bleeding events, clinically relevant non-major bleeding intracranial hemorrhage and minor bleeding events. Bleeding severity will be assessed according to ISTH classification.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Nicolas LELLOUCHE

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Mme Wafa FETHALLAH

Locations

1 EU/EEA country · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications