Withdrawal of Medication in Recovered DCM

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Brief Title

Withdrawal of Medication in Recovered DCM

Official Title

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

Brief Summary

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

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


Primary Outcome

Number of patients that become symptomatic

Secondary Outcome

 Number of patients that drop EF to <45%

Condition

Dilated Cardiomyopathy

Intervention

withdrawal

Study Arms / Comparison Groups

 Treatment
Description:  Withdrawal of beta blockers and ACE inhibitors

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

22

Start Date

February 19, 2016

Completion Date

November 2019

Primary Completion Date

August 24, 2017

Eligibility Criteria

        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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Nadia Giannetti, MD, , 

Location Countries

Canada

Location Countries

Canada

Administrative Informations


NCT ID

NCT02770443

Organization ID

15-284-MUHC


Responsible Party

Principal Investigator

Study Sponsor

McGill University

Collaborators

 McGill University Health Centre/Research Institute of the McGill University Health Centre

Study Sponsor

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


Verification Date

January 2020