Clinical trial NCT02770443: 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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Dilated Cardiomyopathy
Keywords: Recovered LVEF
DCM
Lead sponsor: McGill University
Sponsor class: OTHER
Collaborators: name: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: Jewish General Hospital
First posted: 2016-05-12
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of patients that become symptomatic
timeFrame: 1 year
Secondary outcomes:
measure: Number of patients that drop EF to <45%
timeFrame: 1 year
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
Study officials:
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: Nadia Giannetti, MD
role: PRINCIPAL_INVESTIGATOR
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