Sildenafil Versus Placebo in Chronic Heart Failure

• Status: Unknown status
• Trial end date: 2019-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This protocol describes a 2-arm randomised controlled pilot study assessing the tolerance, safety and efficacy of sildenafil compared to control. The hypothesis is that sildenafil will be well tolerated and efficacious in patients with chronic heart failure (NYHA class II and III) with evidence of systolic dysfunction (EF ≤40 %) and secondary pulmonary hypertension (SPAP >40mmHg).

Patients that satisfy the inclusion criteria will be randomized to sildenafil (40mg x 3) or placebo therapy for 6 months in a 2:1 blinded fashion. The placebo group will be compared to the active therapy group and analysed for differences in the main study end-points Patient Global Assessment and 6-Minute Walk Test.

The study will also assess safety, tolerability, symptoms and quality of life.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Helse Stavanger HF
• Collaborator: Pfizer
• Treatments: Sildenafil Citrate

Criteria

Inclusion Criteria:

1. Men and women

2. 18 - 80 years of age.

3. Outpatients with chronic HF. NYHA class II-III on optimal treatment in sinus rhythm or atrial fibrillation

4. LVEF < 40% measured during the past 12 months

5. SPAP > 40mmHg using echocardiography

6. 6MWTD < 400 meters

7. NT-pro BNP > 400 pg/ml or BNP >100 pg/ml, measured during the past 12 months

8. Receiving optimal therapy, including diuretic, ACE-inhibitor, ARB, beta-blocker and aldosterone antagonist. Doses of all medication should be unchanged during the last 30 days before inclusion.

9. ICDs and CRTs (CRT-P, CRT-D) are permitted. Implantation should have been performed at > 3 months before inclusion to the trial.

Exclusion Criteria:

1. Acute Coronary Syndrome, including myocardial infarction, or coronary angiography, with or without intervention, within the last 3 months

2. Stroke within the last 3 months

3. Planned coronary angiography or planned device-implantation

4. Moderate to severe obstructive valve disease

5. Documented episodes of sustained ventricular tachycardia

6. Oral nitrate therapy or frequent use of sublingual nitrate

7. Concomitant disease which interfere with assessment of dyspnoea , severe COPD, asthma, restrictive lung disease, severe obesity

8. Anemia (hemoglobin < 10g/dL)

9. Uncontrolled hypertension ( SBP >160 mmHg and / or DBP > 90 mmHg)

10. Symptomatic or orthostatic hypotension or systolic blood pressure < 90 mmHg

11. Clinically important renal dysfunction (GFR < 40m ml/min)

12. Women with child-bearing potential

13. Use of

i) alpha-1 antagonist: doxazosin

ii) CYP3A4 inhibitors: erytromycin, ritonavir, sakinovir, itraconazole, ketoconazole

iii) CYP3A4-inducers: rifampicin

iv) Any calcium channel blockers

14. Retinitis pigmentosa, previous diagnosis of NAION (non-arteritic ischemic optic-neuropathy), unexplained visual disturbance.

15. Sickle cell anemia, multiple myeloma, leukemia or penile anatomic deformities (angulation, cavernosal fibrosis, Peyronie's disease) that increases the risk of priapism.

16. Hepatic failure.

17. Drug and alcohol abuse which precludes compliance with the protocol.

18. Inability to understand or sign the written informed consent form of the study,