Sildenafil Versus Placebo in Chronic Heart Failure (SilHF)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Sildenafil in Heart Failure (SilHF); An Investigator Initiated Multinational Randomized Controlled Clinical Trial.|
- Patient Global Assessment [ Time Frame: Baseline, 8 weeks, 24 weeks ] [ Designated as safety issue: No ]Analysis of change from baseline.
- Six minute walk test [ Time Frame: Baseline, 8 weeks, 24 weeks ] [ Designated as safety issue: No ]Analysis of change from baseline.
- Quality of Life (QoL) evaluation by EuroQol5D [ Time Frame: Baseline, 8 weeks and 24 weeks ] [ Designated as safety issue: No ]Analysis of change from baseline.
- Kansas City Questionaire [ Time Frame: Baseline, 8 weeks and 24 weeks ] [ Designated as safety issue: No ]Analysis of change from baseline.
- New York Heart Association (NYHA) function class [ Time Frame: Baseline, 8 weeks, 16 weeks and 24 weeks ] [ Designated as safety issue: No ]Analysis of change from baseline.
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||June 2015|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Active Comparator: Sildenafil
Sildenafil tablets 40 mg x 3 daily
Other Name: Revatio
Placebo Comparator: Placebo
Placebo tablet x 3 daily
Placebo for sildenafil 40mg x 3 daily
Other Name: Placebo
It is estimated that 2-3 % of the adult population suffers from heart failure (HF) and the prevalence is increasing. The European Society of Cardiology (ESC) represents countries with a population > 1,1 billion, and it is estimated that approximately 30 million patients have HF in these 53 countries. Heart failure is particularly prevalent in the elderly population and represents a major burden for both patients and the health services. HF is present in over 10% of patients admitted to hospital and accounts for ~ 2% of national health expenses. Approximately 50% of these costs are related to hospitalisation.
Despite optimal non-pharmacological, pharmacological and device therapy, the morbidity among HF patients is high with symptoms such as dyspnoea and fatigue that reduce quality of life. Following diagnosis approximately 50% are dead after 4 years. Forty percent of patients admitted to hospital with HF are either dead or rehospitalised within one year.
During the last decade, PDE5-inhibitors have been evaluated as a potential treatment for heart failure (see scientific rationale and reference). However, these investigations have been small and there is still limited data. Trials assessing the acute effects of PDE5-inhibition in patients with symptomatic HF due to systolic dysfunction have been performed primarily with sildenafil. Due to the short half-life of sildenafil the drug is administered 3 times daily when studying its chronic effects.
Previous studies have evaluated the 50 mg dose acutely and 50 mg 3 times daily during short-term chronic studies. Importantly, there is considerable off-label use of sildenafil in symptomatic heart failure patients in most European countries.
Revatio is currently licenced for pulmonary hypertension group 1. The dosing scheme is 20mg x 3. However, we suggest targeting a higher dose to achieve optimal clinical benefit in patients with heart failure and moderate congestion. As mentioned above most of the clinical literature in patients with symptomatic heart failure has been done using the 50mg x 3 regimen. However, it is believed that in the proposed study using 40mg x 3 should be equally efficacious. There is already considerable experience using this dosage scheme in heart failure patients locally.
The hemodynamic profile of PDE-5 inhibitors is favourable with reduction in filling pressures, both systemic and pulmonary, vascular resistance accompanied by improvement in symptoms and submaximal and peak exercise performance. This pilot study will evaluate the use of the PDE5-inhibitor sildenafil in patients with heart failure, systolic dysfunction and documented secondary pulmonary hypertension.
|Contact: Trond J Cooper, MD||+47 firstname.lastname@example.org|
|Contact: Kenneth Dickstein, MD, PhD||+47 email@example.com|
|Lady Davis Carmel Medical CEnter||Not yet recruiting|
|Haifa, Israel, 34362|
|Contact: Offer Amir, MD firstname.lastname@example.org|
|Contact: Nabia Salman, MD|
|Principal Investigator: Offer Amir, MD|
|Sub-Investigator: Nabiha Salman, MD|
|Sub-Investigator: Barak Zafrir, MD|
|Sub-Investigator: Michael Gavrieli, MD|
|Rabin Medical Center||Not yet recruiting|
|Petah Tikva, Israel, 49100|
|Contact: Tuvia Ben Gal, MD, PhD email@example.com|
|Contact: Israel Matz, MD|
|Principal Investigator: Tuvia Ben Gal, MD, PhD|
|Sub-Investigator: Israel Matz, MD|
|Sub-Investigator: Andrei Valdman, MD|
|San Donato Hospital||Not yet recruiting|
|Milano, Italy, 20097|
|Contact: Marco Guazzi, MD, PhD firstname.lastname@example.org|
|Contact: Serenella Castelvecchio, MD|
|Principal Investigator: Marco Guazzi, MD, PhD|
|Sub-Investigator: Serenella Castelvecchio, MD|
|Sub-Investigator: Lorenzo Menicanti, MD|
|Stavanger University Hospital||Recruiting|
|Stavanger, Rogaland, Norway, 4011|
|Contact: Trond Cooper, MD +47 51518000 email@example.com|
|Contact: Kenneth Dickstein, PhD +47 51519453 firstname.lastname@example.org|
|Principal Investigator: Trond Cooper, MD|
|Castle Hill Hospital||Not yet recruiting|
|Hull, United Kingdom, HU16 5JQ|
|Contact: John G. Cleland, MD, PhD email@example.com|
|Contact: Mike Lammiman|
|Principal Investigator: John G. Cleland, MD, PhD|
|Northern General Hospital||Not yet recruiting|
|Sheffield, United Kingdom, S5 7AU|
|Contact: Abdallah Al-Mohammad, MD firstname.lastname@example.org|
|Contact: Samantha Maher|
|Principal Investigator: Abdallah Al-Mohammad, MD|
|Principal Investigator:||Kenneth Dickstein, MD, PhD||Helse Stavanger HF|