Sildenafil in US Heart Failure Patients (SilHF-US)

Brief Title

Sildenafil in US Heart Failure Patients (SilHF-US)

Official Title

Sildenafil in US Heart Failure Patients (SilHF-US)

Brief Summary

      This protocol describes a 2-arm randomized 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 analyzed 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.
    

Detailed Description

      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. In United states
      (US) more than 5 million people, or almost 2% of population have HF (Go at al, 2013) Medicare
      data indicate that 12% to 27% of patients hospitalized for heart failure are readmitted
      within 30 days after their discharge, and all-cause mortality reaches 12% in the same period.
      (Jencks at al, 2009).

      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 hospitalized 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 licensed 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 favorable with reduction in filling pressures,
      both systemic and pulmonary, vascular resistance accompanied by improvement in symptoms and
      sub maximal 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.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Six minute walk test

Secondary Outcome

 1.Quality of Life (QoL) evaluation by EuroQol5D

Condition

Heart Failure

Intervention

Sildenafil

Study Arms / Comparison Groups

 Sildenafil 40mgx3 daily
Description:  Sildenafil 40mgx3 daily for 6 months

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

25

Start Date

February 14, 2018

Completion Date

December 2018

Primary Completion Date

December 2018

Eligibility 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 < 475 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. Prior (past 30 days before the baseline visit) or ongoing use of oral nitrate therapy.

          7. Concomitant disease which interfere with assessment of dyspnea , 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. Prior (past 30 days before the baseline visit) or ongoing use of i) alpha-1
             antagonist: doxazosin ii) CYP3A4 inhibitors: erytromycin, ritonavir, sakinovir,
             itrakonazole, ketokonazole iii) CYP3A4-inducers: rifampicin iv) Any calcium channel
             blockers

         14. V) Pulmonary vasodilators at the treatment dose level for Pulmonary
             hypertensionRetinitis pigmentosa, previous diagnosis of NAION (non-arteritic ischemic
             opticus-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,
      

Gender

All

Ages

18 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

Konstadina Darsaklis, MD, 860972-3561, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03460470

Organization ID

HHC-2016-0152


Responsible Party

Principal Investigator

Study Sponsor

Hartford Hospital

Collaborators

 Helse Stavanger HF

Study Sponsor

Konstadina Darsaklis, MD, Principal Investigator, Hartford Hospital


Verification Date

March 2018