Sildenafil in HFpEF (Heart Failure With Preserved Ejection Fraction) and PH

NCT01726049 | Completed Phase 3 Results DMC

• 1 other identifier: Sildenafil Groningen Study
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

Aim of the study is to investigate whether Sildenafil treatment results in a reduction of pulmonary artery pressure without decrease of cardiac output (CO) and in improvement of exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF) with pulmonary hypertension ( PH).

Conditions

Heart Failure, Diastolic; Pulmonary Hypertension

Keywords

HFpEF; PH

Outcome Measures

Primary Outcomes (1)

• Mean Pulmonary Artery Pressure Measured by Right Heart Catheterization

  change of mean pulmonary artery pressure between baseline and 12 weeks measured by heart catheterisation

  baseline and 12 weeks

Secondary Outcomes (3)

• VO2max

  baseline and 12 weeks

• Cardiac Output Measured Invasively by Right Heart Catheterization

  baseline and 12 weeks

• Wedge Pressure Measured Invasively by Right Heart Catheterization

  baseline and 12 weeks

Other Outcomes (1)

• Echocardiographic Parameters of Diastolic LV Dysfunction

  12 weeks

Study Arms (2)

Sildenafil

ACTIVE COMPARATOR

Sildenafil orally 3 times 20mg for 2 weeks , followed by 3 times 60 mg for 10 weeks

Drug: Sildenafil

Placebo

PLACEBO COMPARATOR

placebo orally 3 times 20mg tablets, followed by 3 times 60 mg for 10 weeks

Drug: Placebo

Interventions

Sildenafil DRUG

Sildenafil administered orally 3 times per day 20 mg for the first 2 weeks, followed by 3 times 60 mg for 10 weeks

Sildenafil

Placebo DRUG

Placebo tablets 3 times per day 20 mg foor de first 2 weeks, followed by 3 times 60 mg for 10 weeks

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>18 years
• Written inform consent
• PH secondary to diastolic left heart failure defined as
• PAP mean \>25 mmHg
• Wedge mean \>15 mmHg
• Normal systolic left ventricular (LV) function on echo/nuclear imaging (left ventricular ejection fraction (LVEF) \> or =45%)
• New York Heart Association class (NYHA) II-IV despite heart failure therapy

You may not qualify if:

• Severe noncardiac limitation to exercise (as severe chronic obstructive pulmonary disease)
• Other cause of PH besides diastolic heart failure
• Coronary ischemia or recent myocardial infarction (\<6 months)
• Hypotension ( \<90/50 mmHg)
• Ongoing nitrate therapy
• Ongoing therapy with citochrome P450 3A4 ( CYP3A4) inhibitors (ketoconazole, erythromycin, cimetidine, clarithromycin, itraconazole, voriconazole and protease inhibitors) or CYP3A4 inductors(carbamacepine, phenytoin, phenobarbital, rifampicin, Sint Janskruid ). Furthermore patients will be informed not to drink grapefruit juice while on study medication because of the known impact of grape fruit on pharmacokinetics of Sildenafil.
• Ongoing therapy with alpha -inhibitors
• Significant mitral or aortic valve dysfunction
• Severe liver dysfunction
• Pregnancy
• Unable to read and comprehend Dutch language

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Pfizer: collaborator

Study Sites (1)

University Medical Center Groningen

Groningen, 9700 RB, Netherlands

Location

Related Publications (2)

• Liu LC, Hummel YM, van der Meer P, Berger RM, Damman K, van Veldhuisen DJ, Voors AA, Hoendermis ES. Effects of sildenafil on cardiac structure and function, cardiopulmonary exercise testing and health-related quality of life measures in heart failure patients with preserved ejection fraction and pulmonary hypertension. Eur J Heart Fail. 2017 Jan;19(1):116-125. doi: 10.1002/ejhf.662. Epub 2016 Nov 21.

  PMID: 27873388 DERIVED

• Hoendermis ES, Liu LC, Hummel YM, van der Meer P, de Boer RA, Berger RM, van Veldhuisen DJ, Voors AA. Effects of sildenafil on invasive haemodynamics and exercise capacity in heart failure patients with preserved ejection fraction and pulmonary hypertension: a randomized controlled trial. Eur Heart J. 2015 Oct 7;36(38):2565-73. doi: 10.1093/eurheartj/ehv336. Epub 2015 Jul 17.

  PMID: 26188003 DERIVED

MeSH Terms

Conditions

Heart Failure, Diastolic; Hypertension, Pulmonary

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Heart Failure; Heart Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: E.S. Hoendermis, MD, PHD
• Organization: University Hospital Groningen, NL

e.s.hoendermis@umcg.nl

0031503616161

Study Officials

• E S Hoendermis, MD PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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, PhD

Study Record Dates

• First Submitted: September 21, 2012
• First Posted: November 14, 2012
• Study Start: October 1, 2011
• Primary Completion: September 1, 2014
• Study Completion: December 1, 2014
• Last Updated: March 21, 2016
• Results First Posted: March 21, 2016

Record last verified: 2016-02

Locations

NL (1)