HP 3.1 Sildenafil therapy for pulmonary arterial hypertension (completed)

Multi-center, prospective, randomised, double-blind (open-label from the 26th week onward), placebo-controlled

80 patients

From 4th quarter 2007 to 4th quarter 2012
End of recruitment: 30.05.2010

To demonstrate improved exercise tolerance in patients diagnosed with Eisenmenger’s syndrome as a result of increasing oxygen delivery through the systemic arterial system by progressively lowering pulmonary vascular resistance in the course of treatment

• To demonstrate progressive normalisation of pulmonary arterial function
  (reactivity and vasoactive mediators) in the course of therapy
• Safety and tolerance of the treatment

• Patients aged 14 and over
• Cyanosis with <93% oxygen saturation measured by transcutaneous pulse oximetry
• Clinical indication permitting the invasive diagnostic procedures planned for the study
• Presence of PAH, as diagnosed with invasive methods, with Rp:Rs >0.5, measured at rest, before testing of pulmonary vasodilatatory reserve
• Establishment of one of the following diagnoses:
  a) Anatomically large, congenital, non-corrected shunting defect
  at atrial, ventricular or arterial level
  (PAPVC, ASD, SVD, VSD, AVSD, TAC, APSD, PDA or combination thereof)
  b) Surgically corrected shunting defect (diagnoses as above) with significant residual defect
  c) Other diagnoses with single-ventricle physiology/haemodynamics

Non-specific:

• Contraindication of ergospirometry (treadmill/bicycle)
• Pregnancy/breastfeeding
• Women of childbearing age not practising a reliable method of contraception
• Known or persistent substance abuse (prescription medicines, recreational drugs, alcohol)

Specific:

• Secondary PAH of any other aetiology than that specified in the inclusion criteria
• Known intolerance to NO or iloprost or their constituents
• Acute decompensated heart failure within 7 days before the invasive diagnostic procedure
• Clinically significant haemoptysis in the 6 months preceding the trial
• Haemodynamic instability that would increase the risk of pulmonary arterial reactivity testing
• Arterial hypotension (defined in relation to age)
• Anaemia (Hb < 10 g/dl)
• Decompensated symptomatic polycythaemia
• Thrombocytopenia (< 50,000/µl)
• Secondary impairment of organic function:
  - Impaired creatine clearance (GFR < 30 ml/min/1,73m² BSA)
  - Impaired renal function (ALT and/or AST >3 times normal and bilirubin ≥2 mg/dl)
• Other significant sources of pulmonary blood flow that rule out correct measurement of blood flow to the lungs and hence do not allow reliable calculation of pulmonary vascular resistance:
  - Glenn
  - BT shunt
  - Significant number of MAPCAs
• Obstruction of pulmonary blood outflow:
  - PV obstruction
  - MK dysfunction
• Left ventricular diseases:
  - Affecting the aortal or mitral valve (classed higher than “slight”)
  - Restrictive or congestive cardiomyopathy
  - PCWP/LVEDP >15 mmHg
  - Symptomatic coronary artery disease
• Significant valvular diseases
• Pericardial constriction
• History of stroke, myocardial infarction or life-threatening arrhythmia in the 6 months before screening
• Bronchopulmonary dysplasia (BPD) or other chronic lung diseases
• Significant pulmonary embolism with dominant recalled symptoms
• Other relevant diseases (e.g. HIV infection, diabetes mellitus requiring
  medical treatment)
• Patients with trisomy 21
• Contraindication of sildenafil

• Unspecified or other significant medication (a.o. chronic intake of systemic
  immunosuppression as e.g. systemic glucocorticoids, cytostatic drugs, ciclosporin)
• Drugs to treat pulmonary hypertension, of any delivery form containing PDE-5 antagonists (e.g. sildenafil) or prostanoids (e.g. iIoprost, prostacyclin, beraprost).
  Bosentan (Tracleer®) is explicitly permitted as concomitant medication on condition that it stabilises the patient’s condition and that the patient has been taking bosentan regularly for more than 6 months.
• Drugs that act on vascular function: alpha blockers, L-arginin, ritonavir, nicorandil
• Medication that is not compatible with sildenafil or that interferes with its metabolism: e.g. erythromycin, ketokonazol, itraconazol, protease inhibitors

9 consultations

€2,500 per patient

A number of clinics and heart centres all over Germany are taking part in the study. An up-to-date list of these participants can be found here …