Therapy of PAH – Treatment with Sildenafil in Eisenmenger Patients - Sildenafil

• Register: EUCTR
• Last refreshed on: 31 July 2012
• Main ID: EUCTR2007-002774-64-DE
• Date of registration: 20/08/2007
• Prospective Registration: Yes
• Primary sponsor: Deutsches Herzzentrum Berlin, Kompetenznetz Angeborene Herzfehler
• Public title: Therapy of PAH – Treatment with Sildenafil in Eisenmenger Patients - Sildenafil
• Scientific title: Therapy of PAH – Treatment with Sildenafil in Eisenmenger Patients - Sildenafil
• Date of first enrolment: 04/12/2007
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-002774-64
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no Other trial design description: double blind till week 26, then open (open-label-phase) If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion criteria:
Non-specific
1. Written informed consent obtained.
2. No participation in another AMG driven study attendancing this treatment protocol
Specific
1. Age at least 14 years
2. Presence of cyanosis with < 93 % arterial oxygen saturation (measured by transcutaneous pulse oximetry)
3. Clinical indication for the invasive diagnostic procedures planned for the study is given; this is evaluated on the basis of observation before, during and after medicinal therapy)
4. Presence of PAH as diagnosed by invasive methods with
Rp:Rs > 0.5 measured at rest, before testing of pulmonary vasodilatory reserve
5. One of the following diagnoses:
a) non-corrected large congenital shunting defect at atrial, ventricular or arterial level:
- PAPVD
- ASD
- SVD
- VSD
- AVSD
- TAC
- APW
- PDA
- combinations thereof.
b) Surgically corrected shunting defect (diagnoses as above) with significant residual defect
c) Other diagnoses with univentricular physiology/ hemodynamics.

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Non-specific
1. pregnancy or lactation
2. women of child-bearing age who are sexually active without practising highly effective methods of contraception
3. any diseases or impairment that, in the opinion of the investigator exclude a subject from participation
4. substance abuse (alcohol, medicines, drugs)
5. other medical, psychological or social circumstances that would adversely affect a patient’s ability to participate reliably in the study or increase the risk to themselves or others if they participated
6. insufficient compliance
7. missing willingness to storaging and transferring pseudonymous disease data within this study.
8. subjects who are not able to perform CPX.
Specific:
1. pulmonary hypertension secondary to any etiology other than those specified in the inclusion criteria
2. subjects with known intolerance of NO and iloprost or their constituents
3. acute decompensated heart failure within the 7 days before the invasive diagnostic procedure
4. clinically significant haemoptysis within the last 6 months
5. hemodynamic instability which would represent an unjustifiable risk during testing of pulmonary arterial vasoreagibility
6. arterial hypotension (as defined by age-specific values)
7. anemia (Hb < 10 g/dl)
8. decompensated symptomatic policythemia; (details: 4.2.2. exclusion criteria)
9. thrombocytopenia (< 50.000/µl)
10. secondary impairment of organic function:
- impairment of renal function (GFR < 30 ml/min/1,73 m2 body surface)
- impairment of hepatic function (ALT and/or AST > 3 x ULN and bilirubin = 2 mg/dl)
11. other sources of pulmonary blood flow which prohibit measurement of the blood flow into the lungs and therefore of the pulmonary vascular resistance:
- Glenn
- BT shunt
- significant number of MAPCAs; (details: 4.2.2. exclusion criteria)
12. Obstruction of pulmonary blood outflow:
- obstruction of pulmonary venous return
- mitral valve dysfunction
13. Left heart diseases:
- aortic or mitral valve disease (more severe than “mild”)
- restrictive or congestive cardiomyopathy
- PCWP/LVEDP > 15 mmHg
- symptomatic coronary artery disease
14. Significant valvular diseases other than tricuspid or pulmonary regurgitation (these are not exclusion criteria; details: 4.2.2. exclusion criteria).
15. Pericardial constriction
16. History of stroke, myocardial infarction or life-threatening arrhythmia within the 6 months before screening
17. Bronchopulmonary dysplasia (BPD) and other chronic lung diseases
18. History of significant pulmonary embolism
19. Other relevant diseases (e.g. HIV, diabetes mellitus requiring pharmacologic treatment)
20. Subjects with trisomy 21 (reproducibility of 6-MWT and CPX doubtful; communication as to side effects and subjective quality of life doubtful)
21. all contraindications against the study medication (see also “4.2.3 concomitant medication”)
- hypersensitivity against the active ingredients as well as supplementaries
- patients who lost vision on one eye due to a non arteriitic anterior ischaemic neuropathy of the opticus (NAION).

Prohibited concomitant medication:
Any medication listed below which has not been discontinued at least 30 days prior to screening. Specific pulmonary vasodilators during cardiac catheterization are allowed.
1. Unspecified concomitant medication
2. Other significant medication (e.g. diabetes medication, immunosuppression like glucocorticoids, cytostatics)
3. Instable medication (details: 4.2.5 prohibited concomitant medication):
- begin of a new medica

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patients with pre-existing congenital heart disease may develop Eisenmenger physiology (EP), characterized by development of pulmonary arterial hypertension and intracardiac right to left shunt. This Patients suffer from cyanosis and reduced quality of life. While EP has been regarded as not amenable to conventional treatments, new oral drugs as Sildenafil have been used successfully to improve primary arterial hypertension. Thus may be an important treatment option for patients with EP, too.

Intervention(s)

Trade Name: Revatio
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SILDENAFIL
CAS Number: 139755832
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Improvement of walking distance (during 6- min walking test), oxygen saturation and relation of Rp : Rs during cardiac catheter, described as the difference between visite 1 (baseline) and visite 4 (end of the randomized part of the trial).

Secondary Objective: To provide normalization of pulmonary vascular function (reagibility and vasoactive mediators) in dependence of duration of the Sildenafil-therapy. Changes in Parameters of MRI, Echo-diagnostics and qualitiy of life as well as safety and tolerance of the treatment will be discovered.

Main Objective: To determine the walking distance (during 6- min walking test) and oxygen saturation as well as relation of Rp : Rs during cardiac catheter, described as the difference between visite 1 (baseline) and visite 4 (end of the randomized part of the trial).

Secondary ID(s)

HP 3.1