To determine whether addition of selexipag to current PAH therapy improves exercise capacity, imaging parameters and quality of life, delays time-to-first-PAH-related morbidity and mortality, prevents worsening of World Health Organization…
ID
Source
Brief title
Condition
- Congenital cardiac disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percentage change in exercise capacity (either V*O2peak in cardiopulmonary
exercise test or 6-minute walk distance) between baseline and 6 months of
treatment with selexipag
Secondary outcome
* Time-to-first- PAH-related morbidity event or death by any cause. Morbidity
events defined as any of the following events: disease progression or worsening
of pulmonary arterial hypertension that resulted in hospitalization, initiation
of parenteral prostanoid therapy or long-term oxygen therapy, or the need for
lung transplantation or balloon atrial septostomy. Disease progression was
defined as a decrease in 6-minute walk distance from baseline (>=15%, confirmed
by a 2nd test on a different day) combined with worsening of WHO FC for
patients belonging to WHO FC II/III at baseline, or combined with the need for
additional PAH-specific therapy for patients belonging to WHO FC III/IV at
baseline.
* Onset of (supra)ventricular arrhythmias; supraventricular arrhythmia defined
as an episode of supraventricular bradyarrhythmia or tachyarrhythmia (reported
on (24-hour ambulatory) ECG or requiring change of antiarrhythmic medication,
electrical cardioversion, ablation or pacemaker implantation); ventricular
arrhythmia, defined as nonsustained or sustained ventricular tachycardia,
appropriate implantable cardioverter-defibrillator shock therapy or aborted
ventricular fibrillation.
* Difference of WHO functional class
* Difference right ventricular function parameters with echocardiography
* Difference in serum biomarkers
* Difference in Quality-of-Life scores
* Safety endpoint: number of (serious) adverse events
Background summary
Recently, first-in-class oral drug selexipag has been approved for treatment of
pulmonary arterial hypertension (PAH) in patients with WHO functional class
II-III based on the GRIPHON trial. Unfortunately, patients with pulmonary
arterial hypertension due to congenital heart disease (PAH-CHD) were
underrepresented.
Study objective
To determine whether addition of selexipag to current PAH therapy improves
exercise capacity, imaging parameters and quality of life, delays
time-to-first-PAH-related morbidity and mortality, prevents worsening of World
Health Organization functional class, and reduces biomarker levels in PAH-CHD
patients.
Study design
Open-label, multicenter, randomized, cross-over study
Intervention
Planned treatment: Subjects will receive 2dd individualized maximal tolerated
dose of selexipag for 6 consecutive months.
Study burden and risks
Congenital diagnosis, (surgical) history and current WHO functional class are
recorded at baseline and follow-up. The number of visits will be 4 times: at
baseline (visit 1), after titration phase (visit 2), at 26 weeks (visit 3) and
at 52 weeks (visit 4) follow-up. Visits 1,3 and 4 will each take about 1-1,5
hours; physical examination (10 minutes), electrocardiogram (5 minutes),
laboratory analysis (10 minutes, 9ml) and echocardiography (20 minutes),
cardiopulmonary exercise testing (CPET; 30 minutes) and 6 minute walk test
(6MWT; 15 minutes). Participants are requested to fill-out three questionnaires
related to quality of life. All investigations are part of the regular medical
care according to international guidelines1 and the current standardized
protocol being used in the Academic Medical Center. A large-scaled study has
demonstrated the safety of selexipag. Most commonly reported adverse reactions
are headache, diarrhoea, nausea and vomiting, jaw pain, myalgia and pain in
extremity. The majority of these reactions are of mild to moderate intensity
and are manageable with symptom relieve treatment. As reactions occur more
frequent during the up-titration phase the maximal tolerated dose will be
determined at the end of the titration phase (visit 2; by week 12). The use of
medication by the study population during this study is allowed, and is
recorded.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- Male and female patients * 18 years old
- Symptomatic PAH related to congenital heart disease of all complexities
- WHO functional class II-III
- Documented hemodynamic diagnosis of PAH by right heart catheterization or echocardiography, performed at time prior to screening
- Patients not receiving treatment for PAH or those who are receiving endothelin-receptor antagonist, a phosphodiesterase type 5 inhibitor or both at a dose that has been stable for 3 months
- Signed informed consent
Exclusion criteria
- WHO functional class I of IV
- Patients who have received prostacyclin (analogs) treatment within 1 month before baseline visit or are scheduled to receive any of these drugs during the trial
- Patients with moderate or severe hepatic impairment (Child-Pugh B and C)
- Females who are lactating or pregnant or plan to become pregnant during the study (a pregnancy test is offered to every female patient within the fertile age)
- Known hypersensitivity to any of the excipients of the drug formulations
- Contraindication for trial medication
- Contraindication for cardiopulmonary exercise test
- Incapable of giving informed consent
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 | EUCTR2016-003495-53-NL |
| CCMO | NL59009.018.16 |