NCT03460470

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
25

participants targeted

Target at below P25 for phase_3 heart-failure

Timeline
Completed

Started Feb 2018

Shorter than P25 for phase_3 heart-failure

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 14, 2018

Completed
18 days until next milestone

First Submitted

Initial submission to the registry

March 4, 2018

Completed
5 days until next milestone

First Posted

Study publicly available on registry

March 9, 2018

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2018

Completed
Last Updated

March 9, 2018

Status Verified

March 1, 2018

Enrollment Period

10 months

First QC Date

March 4, 2018

Last Update Submit

March 4, 2018

Conditions

Outcome Measures

Primary Outcomes (2)

  • Six minute walk test

    Analysis of change from the baseline

    Baseline, 8 weeks and 24 weeks

  • Patient Global Assessment (PGA)

    Analysis of change form the baseline

    Baseline; 8 weeks and 24 weeks

Secondary Outcomes (3)

  • 1.Quality of Life (QoL) evaluation by EuroQol5D

    Baseline, 8 weeks and 24 weeks

  • Kansas City Cardiomyopathy Questionnaire (KCCQ)

    Baseline, 8 weeks and 24 weeks

  • New York Heart Association (NYHA) function class

    Baseline, 8 weeks and 24 weeks

Study Arms (2)

Sildenafil 40mgx3 daily

ACTIVE COMPARATOR

Sildenafil 40mgx3 daily for 6 months

Drug: Sildenafil

Placebo tablet x3 daily

PLACEBO COMPARATOR

Placebo for Sildenafil 40mgx3 daily for 6 months

Drug: Placebo oral capsule

Interventions

PDE5 Inhibitor

Sildenafil 40mgx3 daily

Placebo for Sildenafil

Placebo tablet x3 daily

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Men and women
  • years of age.
  • Outpatients with chronic HF. NYHA class II-III on optimal treatment in sinus rhythm or atrial fibrillation
  • LVEF ≤ 40% measured during the past 12 months
  • SPAP ≥ 40mmHg using echocardiography
  • MWTD \< 475 meters
  • NT-pro BNP ≥ 400 pg/ml or BNP ≥100 pg/ml, measured during the past 12 months

You may not qualify if:

  • Acute Coronary Syndrome, including myocardial infarction, or coronary angiography, with or without intervention, within the last 3 months
  • Stroke within the last 3 months
  • Planned coronary angiography or planned device-implantation
  • Moderate to severe obstructive valve disease
  • Documented episodes of sustained ventricular tachycardia
  • Prior (past 30 days before the baseline visit) or ongoing use of oral nitrate therapy.
  • Concomitant disease which interfere with assessment of dyspnea , severe COPD, asthma, restrictive lung disease, severe obesity
  • Anemia (hemoglobin \< 10g/dL)
  • Uncontrolled hypertension ( SBP \>160 mmHg and / or DBP \> 90 mmHg)
  • Symptomatic or orthostatic hypotension or systolic blood pressure \< 90 mmHg
  • Clinically important renal dysfunction (GFR \< 40m ml/min)
  • Women with child-bearing potential
  • 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
  • V) Pulmonary vasodilators at the treatment dose level for Pulmonary hypertensionRetinitis pigmentosa, previous diagnosis of NAION (non-arteritic ischemic opticus-neuropathy), unexplained visual disturbance.
  • Sickle cell anemia, multiple myeloma, leukemia or penile anatomic deformities (angulation, cavernosal fibrosis, Peyronie's disease) that increases the risk of priapism.
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hartford Hospital 80 Seymour street

Hartford, Connecticut, 06102, United States

RECRUITING

Related Publications (2)

  • Guazzi M, Dickstein K, Vicenzi M, Arena R. Six-minute walk test and cardiopulmonary exercise testing in patients with chronic heart failure: a comparative analysis on clinical and prognostic insights. Circ Heart Fail. 2009 Nov;2(6):549-55. doi: 10.1161/CIRCHEARTFAILURE.109.881326. Epub 2009 Sep 28.

  • Cooper TJ, Guazzi M, Al-Mohammad A, Amir O, Bengal T, Cleland JG, Dickstein K. Sildenafil in Heart failure (SilHF). An investigator-initiated multinational randomized controlled clinical trial: rationale and design. Eur J Heart Fail. 2013 Jan;15(1):119-22. doi: 10.1093/eurjhf/hfs152. Epub 2012 Oct 24.

MeSH Terms

Conditions

Heart FailureHypertension, Pulmonary

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Heart DiseasesCardiovascular DiseasesLung DiseasesRespiratory Tract DiseasesHypertensionVascular Diseases

Intervention Hierarchy (Ancestors)

SulfonamidesAmidesOrganic ChemicalsSulfonesSulfur CompoundsPiperazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Konstadina Darsaklis, MD

    Hartford Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Arben Ademi, CCRP

CONTACT

Konstadina Darsaklis, MD

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

March 4, 2018

First Posted

March 9, 2018

Study Start

February 14, 2018

Primary Completion

December 1, 2018

Study Completion

December 1, 2018

Last Updated

March 9, 2018

Record last verified: 2018-03

Data Sharing

IPD Sharing
Will share

The SilHF trial is an international, multi-centre effort with five participating European centres.The Steering Committee of the SilHF trial, has elected to pool the individual patient data from the five European centers with a large single center in Hartford Connecticut, USA, PI: Konstadina Darsaklis. The US site will follow an identical protocol to the European sites and enter data on the electronic case report form to the data management centre in Trondheim, Norway. We intend to perform the meta-analysis independent of the results of the separate studies. All sites have obtained the required regulatory approvals.

Shared Documents
STUDY PROTOCOL, SAP, CSR
Time Frame
The only US site at Hartford Hospital will complete enrollment by the end of year 2018. Data will be available and study database will be updated within 5 days of any obtained f-u visit.
Access Criteria
De-identified coded data will be entered into a secure login study database.

Locations