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

RE-ELECT Study: "Randomized Evaluation of Changing Kidney Function Over a Time in Patients With Atrial Fibrillation (AF), Concomitant T2DM and Existing Chronic Kidney Disease (CKD) Treated With Dabigatran or Warfarin for Stroke Prevention"

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Diseases; Atrial Fibrillation; T2DM (Type 2 Diabetes Mellitus)
• Intervention / Treatment: Drug: Dabigatran Etexilate

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

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Dmitry Napalkov; Phone Number: +79104520841; Email: dminap@mail.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 119991
    • Recruiting
    • I.M.Sechenov First Moscow State Medical University (Sechenov University)
    • Contact: Dmitry Napalkov; Phone Number: +79104520841; Email: dminap@mail.ru
    • Contact: Anastasia Sokolova; Phone Number: +79036135898; Email: sokolovastasya2@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dabigatran etexilate; Dabigatran etexilate (Pradaxa) 110 mg b.i.d. or 150 mg b.i.d. according SmPC during 2 years	Drug: 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; Other Names: Pradaxa
ACTIVE_COMPARATOR: Warfarin; Warfarin under the control of INR once a month (target range 2.0 - 3.0) during 2 years	Drug: 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; Other Names: Pradaxa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in annual eGFR decline (slopes) between dabigatran and warfarin patients	eGFR is to be calculated with CKD-EPI equation at baseline and at subsequent major visits.; for primary analysis only eGFR levels at one year and second year of treatment will be used. In case of one of values required for the analysis is missed LOCF (last observational carried forward) approach will be used	2 years

Collaborators and Investigators

• Sponsor: Irina Ermolaeva
• Investigators: Principal Investigator: Dmitry Napalkov, First Moscow State Medical University (Sechenov's University)

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 14, 2018
• Primary Completion (ANTICIPATED): July 1, 2021
• Study Completion (ANTICIPATED): May 1, 2022

Study Registration Dates

• First Submitted: December 27, 2018
• First Submitted That Met QC Criteria: December 27, 2018
• First Posted (ACTUAL): December 31, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 26, 2021
• Last Update Submitted That Met QC Criteria: March 23, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Mellitus; Renal Insufficiency; Arrhythmias, Cardiac; Diabetes Mellitus, Type 2; Kidney Diseases; Renal Insufficiency, Chronic; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran
• Other Study ID Numbers: 1160.283

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