Heart FailurePhase 3SilHF-USNCT03460470
Sildenafil in US Heart Failure Patients (SilHF-US)
A Phase 3 study testing Sildenafil in people with Heart Failure and Pulmonary Hypertension, run by Hartford Hospital at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Heart Failure, Pulmonary Hypertension
- What is being tested?
- Sildenafil
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Feb 2018to Dec 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women
- 18 - 80 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
- 6MWTD < 475 meters
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- NT-pro BNP ≥ 400 pg/ml or BNP ≥100 pg/ml, measured during the past 12 months
- 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.
- ICDs and CRTs (CRT-P, CRT-D) are permitted. Implantation should have been performed at > 3 months before inclusion to the trial.
Who cannot join
- 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.
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- 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.
- Hepatic failure.
- Drug and alcohol abuse which precludes compliance with the protocol.
- Inability to understand or sign the written informed consent form of the study,
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Hartford Hospital 80 Seymour street
Hartford, Connecticut, 06102
Konstadina Darsaklis, MD, 860-972-1212, konstadina.darsaklis@hhchealth.org
Arben Ademi, CCRP, 860-972-3561, arben.ademi@hhchealth.org
About this study
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.
Read the 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.
- Conditions
- Heart Failure, Pulmonary Hypertension
- Being tested
- Sildenafil, Placebo oral capsule
- Medical subject headings
- Heart Failure, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
PDE5 Inhibitor
Placebo oral capsuleDrug
Placebo for Sildenafil
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil 40mgx3 daily | Active comparator | Sildenafil 40mgx3 daily for 6 months Receives: Drug: Sildenafil |
| Placebo tablet x3 daily | Placebo comparator | Placebo for Sildenafil 40mgx3 daily for 6 months Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Six minute walk test
Analysis of change from the baseline
Measured: Baseline, 8 weeks and 24 weeks
Patient Global Assessment (PGA)
Analysis of change form the baseline
Measured: Baseline; 8 weeks and 24 weeks
Secondary outcomes (3)
1.Quality of Life (QoL) evaluation by EuroQol5D
Analysis of change from baseline
Measured: Baseline, 8 weeks and 24 weeks
Kansas City Cardiomyopathy Questionnaire (KCCQ)
Analysis of change from baseline
Measured: Baseline, 8 weeks and 24 weeks
New York Heart Association (NYHA) function class
Analysis of change from baseline
Measured: Baseline, 8 weeks and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2018
- Study start14 Feb 2018
- Primary completionDec 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hartford Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Helse Stavanger HF
- Responsible party
- Principal investigator, Konstadina Darsaklis, Hartford Hospital
- Investigators
- Konstadina Darsaklis, MD, Principal investigator, Hartford Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03460470
- Sponsor's protocol ID
- HHC-2016-0152
- Acronym
- SilHF-US
- Status last verified
- Mar 2018
- First submitted
- 4 Mar 2018
- Last updated
- 9 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 19919979Cooper 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.
PubMed 23097067
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sildenafil in US Heart Failure Patients (SilHF-US)
- ClinicalTrials.gov ID
- NCT03460470
- Acronym / sponsor ID
- SilHF-US / HHC-2016-0152
- Conditions
- Heart Failure, Pulmonary Hypertension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Hartford HospitalUniversity, hospital or other
- Collaborators
- Helse Stavanger HF
- Study start
- 14 Feb 2018 (actual)
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 9 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sildenafil 40mgx3 daily | Active comparator | Drug: SildenafilSildenafil 40mgx3 daily for 6 months |
| Placebo tablet x3 daily | Placebo comparator | Drug: Placebo oral capsulePlacebo for Sildenafil 40mgx3 daily for 6 months |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Men and women
- 18 - 80 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SildenafilPDE5 Inhibitor | Drug | Sildenafil 40mgx3 daily |
| Placebo oral capsulePlacebo for Sildenafil | Drug | Placebo tablet x3 daily |
Primary outcome
Six minute walk test
Time frame: Baseline, 8 weeks and 24 weeks
Analysis of change from the baseline
Patient Global Assessment (PGA)
Time frame: Baseline; 8 weeks and 24 weeks
Analysis of change form the baseline
3 secondary outcomes
1.Quality of Life (QoL) evaluation by EuroQol5D
Time frame: Baseline, 8 weeks and 24 weeks
Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time frame: Baseline, 8 weeks and 24 weeks
New York Heart Association (NYHA) function class
Time frame: Baseline, 8 weeks and 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2018.
- Results publication: PubMed 19919979Guazzi 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.
- Results publication: PubMed 23097067Cooper 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Konstadina Darsaklis, MD principal investigator
Hartford Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sildenafil in people with Heart Failure and Pulmonary Hypertension, run by Hartford Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Arben Ademi, CCRP (860972-3561, arben.ademi@hhchealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Six minute walk test (time frame: Baseline, 8 weeks and 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03460470, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2018.