Withdrawal of Medication in Recovered DCM (WrecEF)

January 21, 2020 updated by: Nadia Giannetti, McGill University

Withdrawal of Beta- Blockers and ACE Inhibitors After Left Ventricular Systolic Function Recovery in Patient With Dilated Cardiomyopathy: A Randomized Control Trial.

Randomized study of medication withdrawal in patients who have recovered LV function in Dilated Cardiomyopathy.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Importance of the study:

There is a growing population of patients with dilated cardiomyopathy (DCM) who had recovered left ventricular (LV) systolic function on medical therapy. Recent studies have shown a favorable clinical course in patients with DCM1-4. The heart failure (HF) guidelines states that discontinuation of medical therapy in this group of patients may be considered based on expert opinion. The safety of withdrawal of medical therapy needs further studies.

Hypothesis:

In Patients with dilated cardiomyopathy (DCM) who had recovery of the LV systolic function to a normal EF >50%, medical therapy withdrawal is attainable without Clinical deterioration or recurrence of LV systolic dysfunction.

Objective

  1. To study the withdrawal of guideline directed medical therapy, specifically beta-blockers and ACE/ARB, in patients with DCM after recovery of LV EF.
  2. Correlate the sustained recovery in LVEF after medication discontinuation with specific genetic markers of recovery.

Method:

Study design:

It is a multi-center, non-blinded, randomized Control trial (pilot) comparing withdrawal of medical therapy in patients with recovered LVEF (recEF) compared to patients continuing medical therapy. Therapeutic changes will occur in a 2:1 randomization at the Royal Victoria Hospital, the Montreal General Hospital and the Jewish General Hospital. Patient would be recruited from a Heart Function Clinic or the echocardiography lab.

Procedures:

Patient Selection:

Patient selection will be conducted through chart review, ECHO lab, as well as the clinical visits. The DPS authorization will be requested.

Informed consent:

At time of enrolment the study's objective, procedures as well as the risks and benefits will be explained to the patient. A consent form will be provided to the patient. In addition, a wallet card and a medication discontinuations chart.

Randomization:

Randomization will be conducted in 2:1 fashion, non-blinded, through a sealed envelop randomization system.

Medical therapy withdrawal:

Medical therapy withdrawal will be conducted in 2 phases.

Phase 1:

This phase involves the withdrawal of the beta-blocker. The patient will be followed for signs of deterioration for a period of 6 months following the withdrawal.

Phase 2:

If there are no signs of deterioration the ACE/ARB inhibitor will be withdrawn as well. The patient will be followed up in 6 month for signs of deterioration. All other medical therapies other than beta-blocker and ACE inhibitors will continue until successful withdrawal of beta-blockers and ACE inhibitor is achieved.

Beta-blocker discontinuation:

The initial tapering off will occur over a 2week period. The beta -blocker will be discontinued by the end of the 2nd week.

For example: Metoprolol 100mg bid to Metoprolol 75mg bid for 5days. Followed by Metoprolol 50mg bid for 4 days, then Metoprolol 25 mg for 3 days and then completely discontinued.

ACE/ARB discontinuation:

The discontinuation of ACE/ARB will be similar to the beta-blockers. The doses will be tapered over a two-week period.

A supplementary chart of dose reduction is provided. The doses included are the standard medication doses.

Digoxin, diuretic, spironolactone will be discontinued if both the beta-blocker and ACE-ARB discontinuation has been well tolerated or if a clinical indication warrants the discontinuation. Up titration of therapies will not be permitted.

Additional therapy for SBP > 130 or DBP >80mmHg with non-ACE or beta blocker therapy will be considered.

Genotyping: Genetic analysis for DCM causing gene will be sent for the study patients. The genotyping is selective, patient will have the option to opt out the genetic analysis if they do not prefer having a genotyping done. All samples will be stored in a bio bank to maximum of 25 years. Two comparisons will be conducted on the genotyping:

  1. The genetic typing for Patients with improved EF will be compared to the control group from the ongoing DCM cohort at the McGill University Health Center.
  2. A second comparison between the patients within the withdrawal cohort. A comparison will be made between patients with rebound HF and the patient who did not HF with discontinuation of medical therapy.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3A 3J1
        • Royal Victoria Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  1. Patient diagnosed with dilated cardiomyopathy (DCM) with an initial HFrEF < 40 % at presentation.
  2. DCM with recovered LV function to > or = to 50% documented on 2 ECHO examinations, with the most recent ECHO examination within 1 year of enrolment.
  3. Time from initial diagnosis of DCM more or equal to 24 month.
  4. Last hospitalization for decompensated HF > 1year.

Exclusion criteria:

  1. Ischemic cardiomyopathy
  2. Other structural pathology such as: Hypertrophic cardiomyopathy, Valvular cardiomyopathy or congenital heart disease.
  3. Last hospitalization for decompensated HF < 1year ago.
  4. Previous sustained ventricle tachycardia or ventricle fibrillation (VF) arrest.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment
Withdrawal of beta blockers and ACE inhibitors
Drug: withdrawal
withdrawal of beta blocker and ACE inhibitors
Other Names:
  • withdrawal ACE and beta blockers
  • discontinuation of ACE and beta blockers
Placebo Comparator: control
no withdrawal, standard of care
Drug: standard of CARE
STANDARD OF CARE, NO WITHDRAWAL OF MEDICAL THERAPY

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of patients that become symptomatic
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of patients that drop EF to <45%
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

McGill University

Collaborators

McGill University Health Centre/Research Institute of the McGill University Health Centre
Jewish General Hospital

Investigators

  • Principal Investigator: Nadia Giannetti, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 19, 2016

Primary Completion (Actual)

August 24, 2017

Study Completion (Actual)

November 1, 2019

Study Registration Dates

First Submitted

April 29, 2016

First Submitted That Met QC Criteria

May 11, 2016

First Posted (Estimate)

May 12, 2016

Study Record Updates

Last Update Posted (Actual)

January 23, 2020

Last Update Submitted That Met QC Criteria

January 21, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15-284-MUHC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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