RE-ELECT. Dabigatran vs Warfarin in AF Patients With T2DM and CKD

NCT ID: NCT03789695

Last Updated: 2021-03-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-14
• Study Completion Date: 2022-05-31

Brief Summary

Kidney function in patients with atrial fibrillation (AF) is tending to decline over a time which is clearly demonstrated in clinical studies. Renal impairment is a risk factor for stroke, its progression is associated with unfavorable prognosis. So preserving kidney function should be considered as a one of priorities when choosing treatment strategies which is especially important in patients with existing chronic kidney disease (CKD) or in patients who have risk of its development. This is especially relevant for the patients with type 2 diabetes mellitus (T2DM) and with CKD who can be considered as a group of risk for rapid kidney function decline.

Detailed Description

It is suggested that the decline in renal function may occur more slowly in patients receiving dabigatran etexilate (Pradaxa) compared to patients taking warfarin. The planned trial is a prospective phase IV randomized trial in which patients with AF, T2DM and CKD will be randomized to groups receiving either dabigatran etexilate (Pradaxa) or warfarin. The main goal of the study is to assess the differences in annual eGFR reduction between patients receiving dabigatran etexilate (Pradaxa) or warfarin for 24 months. The difference in annual eGFR reduction will be estimated using the SMPI parameters (mixed model of repeated measurements). Secondary goals are as follows: - to evaluate the progression of albuminuria during treatment with dabigatran etexilate (Pradaxa) or warfarin based on the combined endpoint; - to evaluate the dynamics of the albumin/creatinine ratio (ACR) in urine during 2 years of treatment with dabigatran etexilate (Pradaxa) or warfarin; - to evaluate bleeding episodes, acute cerebrovascular accident, and systemic embolism in the dabigatran etexilate (Pradaxa) and warfarin groups; - to compare glycemic control (HbA1c) in patients receiving dabigatran etexilate (Pradaxa) and warfarin

Conditions

Atrial Fibrillation; T2DM (Type 2 Diabetes Mellitus); Chronic Kidney Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Dabigatran etexilate

Dabigatran etexilate (Pradaxa) 110 mg b.i.d. or 150 mg b.i.d. according SmPC during 2 years

Group Type: EXPERIMENTAL

Dabigatran Etexilate

Intervention Type: DRUG

Study drug dabigatran etexilate. There are two dosage regimens of dabigatran etexilate used in the study: 150 mg b.i.d. and 110 mg b.i.d. The dose of dabigatran etexilate will be chosen by the investigator in accordance with Russian PRADAXA SmPC

Warfarin

Warfarin under the control of INR once a month (target range 2.0 - 3.0) during 2 years

Group Type: ACTIVE_COMPARATOR

Dabigatran Etexilate

Intervention Type: DRUG

Study drug dabigatran etexilate. There are two dosage regimens of dabigatran etexilate used in the study: 150 mg b.i.d. and 110 mg b.i.d. The dose of dabigatran etexilate will be chosen by the investigator in accordance with Russian PRADAXA SmPC

Interventions

Dabigatran Etexilate

Study drug dabigatran etexilate. There are two dosage regimens of dabigatran etexilate used in the study: 150 mg b.i.d. and 110 mg b.i.d. The dose of dabigatran etexilate will be chosen by the investigator in accordance with Russian PRADAXA SmPC

Intervention Type: DRUG

Other Intervention Names

Pradaxa

Eligibility Criteria

Inclusion Criteria

• Non-valvular atrial fibrillation
• Diagnosis of T2D according to Russian Clinical Guidelines
• Chronic kidney disease according to KDIGO definition*
• Stable RAS background treatment
• Age > 18 yrs;
• Informed consent to participate in the study signed by the patient.

Exclusion Criteria

• HbA1c >10%
• UACR > 3000
• Renal transplant
• Biopsy proven kidney entities other than Diabetic Kidney Disease (if known only, no kidney biopsy is planned within the study)
• Background immunosuppressant therapy
• Hematologic disorders which can influence hemostasis (hemoblastosis, etc.); connective tissue diseases (SLE, systemic scleroderma, dermatomyositis) and any vasculitis;
• Primary or secondary antiphospholipid syndrome;
• Known cancer diagnosis;
• Major surgical interventions within 3 months before the study enrollment and planned for the timelines of the study;
• Clinically relevant bleeding events within 3 months before the study enrollment;
• Acute coronary syndrome, PCI or CABG within 12 months before the study enrollment;
• Hemorrhagic stroke within 12 months before the study enrollment;
• Organ damages resulted from clinically relevant bleeding within 6 months before randomization
• Major trauma or any craniocerebral trauma within 30 days before randomization
• Uncontrolled hypertension (systolic BP>180 and or diastolic BP>100 while on antihypertensive treatment)
• CHF III-IV functional class (by NYHA)
• Ischemic stroke within the last 14 days before randomization
• Concomitant aspirin and/or clopidogrel use;
• Persistent use of drugs with potential nephrotoxic effects (NSAIDs, cytotoxic drugs etc.);
• Need in anticoagulation treatment for disease other than AF
• Pregnancy and lactation;
• Creatinine clearance < 30 ml/min (by Cockroft - Gault equation)
• Thrombocytopenia of <100 *109 /л
• Hepatic failure B and C by Child-Pugh score
• Psychiatrist disorders
• Background poor compliance
• Known hypersensitivity to dabigatran, warfarin or their components
• Life expectancy less than two years

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

Sponsors

Irina Ermolaeva

OTHER

Sponsor Role: lead

Responsible Party

Irina Ermolaeva

Head of Department of preclinical and clinical trials management

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Dmitry Napalkov

Role: PRINCIPAL_INVESTIGATOR

First Moscow State Medical University (Sechenov's University)

Locations

I.M.Sechenov First Moscow State Medical University (Sechenov University)

Moscow, , Russia

Site Status: RECRUITING

Countries

Russia

Central Contacts

Dmitry Napalkov

Role: CONTACT

dminap@mail.ru

+79104520841

Facility Contacts

Dmitry Napalkov

Role: primary

dminap@mail.ru

+79104520841

Anastasia Sokolova

Role: backup

sokolovastasya2@gmail.com

+79036135898

Other Identifiers

1160.283

Identifier Type: -

Identifier Source: org_study_id