Clinical trial NCT01463800: Rehabilitation in Patients With Congenital Heart Disease
Official title: Cardiac Rehabilitation in Patients With Complex Congenital Heart Disease: Improvement of Exercise Intolerance
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Heart Defects, Congenital
Keywords: Heart Defects, congenital
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2011-11-02
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: Exercise intolerance is a major burden for patients with complex congenital heart disease (CHD), significantly affecting their quality of life. Cardiopulmonary exercise testing provides a reliable tool both for assessing exercise capacity of CHD patients and for risk stratification and is becoming part of the routine clinical assessment of these patients. Exercise has an effect on the muscular, metabolic and circulatory systems. While exercise training has been widely studied in chronic heart failure, its efficacy in adults with CHD remain unknown. The investigators hypothesize that structured exercise training will improve exercise intolerance, in particular peak VO2. The aim of this multicenter, randomized study is to evaluate the impact of structured exercise training on exercise intolerance in patients with complex CHD.

Detailed description: This is a randomized, prospective, multicenter, interventional study.

After study patients have given written consent they will be randomized either in the interventional group with a rehabilitation program or in the control group without rehabilitation program. Patients who are randomized in the control group are allowed to perform the rehabilitation program 12 months after randomisation. Patients in the interventional group will perform structured exercise training on 3 weekdays during a 12-weeks period. Training will be performed by ergometer and low-impact gymnastic and relaxation training.

All study participants have the following investigations at the beginning of the study and after 12 weeks:

* Cardiopulmonary exercise testing with spirometry
* 6-minute walk test
* Blood work: BNP, Creatinine, Sodium, Potassium, Urat, Cholesterol (HDL-L and LDL-L)
* Validated Heart failure questionnaires (SF-36 and Minnesota Living with heart failure questionnaire, German version for Basel, Zürich and Bern) All tests will be repeated as clinically indicated in a follow-up visit 12 months after baseline

Primary outcome is:

Comparison of peak VO2 at the end of rehabilitation between both groups.

Secondary outcomes are:

* Comparison of 6-min walk test, VE/VCO2 slope, anaerobic threshold and heart rate and blood pressure response after rehabilitation between both groups
* Changes of 6-min walk test, peak VO2, VE/VCO2 slope, anaerobic threshold and heart rate and blood pressure response at the end and 12 months after rehabilitation.
* Changes of quality-of-life assessed by validated heart failure questionnaire at the end and 12 months after rehabilitation and comparison between both groups.
* Changes of levels of brain-natriuretic peptide at the end and 12 months after rehabilitation.
* Adverse events during rehabilitation including new onset of arrhythmia, admission due to worsening heart failure or death.

The calculated sample size to reach a power of 0.80 is 83 patients in each arm. Patients with complex CHD and exercise intolerance are at increased risk for premature death and severe cardiac complications including arrhythmia needing treatment, heart failure and circulatory failure, pulmonary hemorrhage, pulmonary embolism and endocarditis. Hence, the likelihood of major adverse cardiac events during the study phase is considerably high. However, there is no evidence of functional worsening by low-level exercise. Smaller studies with patients with congenital heart disease and/or pulmonary hypertension did not report safety issues. Although sudden cardiac death is one of the leading modes of death in this population, it is extremely rare that sudden death occurs during exercise. Cardiac patients who are at specific risk for exercise-induced arrhythmia are not included into the study (i.e. patients with hypertrophic obstructive cardiomyopathy).

Eligibility criteria: Inclusion Criteria:

1. Patients with complex CHD including cyanotic heart disease, subaortic right ventricle physiology, single ventricle physiology, Ebstein anomaly with ≥ moderate tricuspid regurgitation and patients with Tetralogy of Fallot (including those with pulmonary atresia of Fallot type or double-outlet right ventricle of Fallot type) and either residual free pulmonary regurgitation or left- or right ventricular systolic dysfunction (demonstrated by echocardiography or cardiac MRI).
2. Peak VO2 \< 85% of predicted (standardized for age, gender, weight and height) obtained by cardiopulmonary exercise testing
3. Sedentary lifestyle (\< 30 minutes of regular exercise per week)

Exclusion Criteria:

1. Patients with dyspnea New York Heart Association (NYHA) class IV.
2. Severe left ventricular outflow tract obstruction.
3. Unstable angina or recent myocardial infarction (\<12 months).
4. Uncontrolled ventricular arrhythmia.
5. Recent intervention (\<12 months)
6. Life expectancy \<12 months
7. No consent.

Primary outcomes:
measure: peak VO2
timeFrame: 12 weeks
Secondary outcomes:
measure: 6 minute walk test
timeFrame: 12 weeks
measure: VE/VCO2
timeFrame: 12 weeks
measure: heart rate response
timeFrame: 12 weeks
measure: QoL
timeFrame: 12 weeks
measure: BNP
timeFrame: 12 weeks
measure: Adverse events
timeFrame: 12 weeks
measure: peak VO2
timeFrame: 12 months
measure: VE/VCO2
timeFrame: 12 months
measure: Heart rate response
timeFrame: 12 months
measure: 6 minute walk test
timeFrame: 12 months
measure: QoL
timeFrame: 12 months
measure: BNP
timeFrame: 12 months
measure: Cardiac adverse events
timeFrame: 12 months
Other outcomes:
Locations:
city: Sevilla
country: Spain
facility: Virgen Macarena University Hospital
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Zurich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Daniel Tobler, MD
role: PRINCIPAL_INVESTIGATOR
References: