Identify congenital heart disease patients with exercise-induced pulmonary arterial hypertension. Analyze changes in pulmonary arterial pressures at peak exercise in patients with exercise induced pulmonary arterial hypertension before and after…
ID
Source
Brief title
Condition
- Congenital cardiac disorders
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine:
• change in mean pulmonary arterial pressure (mPAP) at peak exercise
o measured by means of transthoracic echocardiography at 3 and 6 months
followup: mPAP = 0.6 x systolic PAP.
o peak exercise is defined as 80% of maximum calculated heart rate: peak
exercise=0.8*(220-age)
Secondary outcome
To determine:
• Cardiopulmonary exercise capacity (i.e. peak oxygen consumption, VE/VCO2
ratio, O2 pulse)
• Pulmonary hemodynamics (i.e. systolic pulmonary arterial pressure, pulmonary
vascular resistance, pressure-flow relationships during and at peak exercise)
• Right ventricular function (i.e. TAPSE, TEI index, TDI-S, right ventricular
dimensions)
• Laboratory parameters (i.e. NT-pro BNP, troponin T)
• NYHA functional class
• Quality of life (assessed by TAAQOL-CHD, SF-36 and Minnesota CHD-HF
questionnaire)
• Demographics (age, gender, marital status, work, income); assessed by
demographic questionnaire.
Background summary
Pulmonary arterial hypertension (PAH) can be a rapidly progressive disorder and
is associated with a high mortality rate, despite medical intervention. With
the availability of effective therapy, early disease detection is an important
strategic objective to improve treatment outcomes. Resting echocardiography is
currently the recommended screening modality for high-risk population groups.
However, it is clear that abnormalities in resting hemodynamics (and symptoms)
are late sequelae of the pathobiological processes that begin in the distal
pulmonary arteries. Exercise stress may unmask early pulmonary vascular
dysfunction, however the definition, clinical significance, and natural history
of *exercise PAH* remain undefined. However, based on clinical experience and
literature the prevalence is estimated at ~ 20%.Treatment with endothelin
receptor blockers has shown a beneficial influence on the clinical performance
in patients with exercise induced PAH due to systemic sclerosis and primary
pulmonary hypertension. Whether endothelin receptor blockers decrease pulmonary
pressures and improve clinical outcome in patients with exercise induced
pulmonary arterial hypertension due to congenital heart disease is unknown.
Study objective
Identify congenital heart disease patients with exercise-induced pulmonary
arterial hypertension. Analyze changes in pulmonary arterial pressures at peak
exercise in patients with exercise induced pulmonary arterial hypertension
before and after treatment with bosentan, compared to placebo.
Study design
Randomized placebo controlled trial with a study period of 26 weeks.
Intervention
After randomization one group (n=20) receives a 125 mg tablet of Bosentan twice
daily for 6 months. The other group (n=20) receives placebo for 6 months.
Study burden and risks
All investigations, blood analysis excepted, are non-invasive and free of risk.
The burden for the patients mainly consists of the time that is consumed by the
investigations, namely: history taking + physical examination (15 min);
Quality-of-Life- score (15 min); demographic questionnaire (5min); laboratory
tests (electrolytes, creatinine, urea, albumin and neurohormones, troponin T)
(5min); 12 lead electrocardiogram (10 min); exercise echocardiography (45 min);
cardiovascular exercise testing (30 min).
The trial medication has a potential risk of liver damage, which will be
monitored regularly by laboratory testing of liver transaminases.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- adult (>18 years) and mentally competent
- Open or closed septal defect (ASD I/II, VSD, AVSD)
- Open or closed systemic-to-pulmonary shunt (PDA)
- Negative pregnancy test
- Presence of X-PAH, including one of the following criteria, at peak exercise.
* mPAP > 34 mmHg with CO <= 10 l/min
* mPAP > 40 mmHg with CO <= 15 l/min
* mPAP > 45 mmHg with CO <= 20 l/min
* mPAP > 50 mmHg with CO <= 30 l/min
* PVR (slope pressure/flow plot) of > 2.5 mmHg/l/min during exercise
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
- Incapable of giving informed consent
- Pregnancy or lactation (a pregnancy test is offered to every female patient within fertile age)
- Women of child-bearing age who are sexually active without practising reliable methods of contraception. The use of oral contraceptives only, is not considered reliable.
- Substance abuse (alcohol, medicines, drugs)
- Subjects who are not able to perform cardiopulmonary exercise testing
- Any cardiac operation <6 months before inclusion
- PAH of any aetiology other than the one specified in the inclusion criteria
- Left ventricular ejection fraction < 30%
- Significant impairment of renal function (GFR < 30 ml/min/1.73m2)
- Moderate to severe liver disease: Child Pugh class B or C
- Raised plasma transaminases level > three times upper normal limit
- Arterial hypotension (systolic blood pressure < 85mmHg)
- Anaemia (Hb < 10g/L, or <6.21 mmol/L)
- Significant valvular disease, other than tricuspid or pulmonary regurgitation
- Chronic lung disease or total lung capacity < 80% predicted value
- History of significant pulmonary embolism
- Other relevant diseases (HIV infection, Hep B/C infection)
- Subjects with known intolerance to bosentan or their constituents
- Prohibited medication: any medication listed below which has not been discontinued at least 30 days prior to inclusion
o Unspecified or other significant medication (glybenclamide or immunosuppression)
o PAH therapy (endothelin receptor antagonists, PDE-5 inhibitors, prostanoids)
o Medication which is not compatible with bosentan or interferes with its metabolism (inhibitors or inducers of CYP2C9, CYP3A4) or medication which may interfere with bosentan treatment according to the investigator
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-004067-41-NL |
| CCMO | NL42568.018.12 |