Recruiting
Phase 3

Sildenafil

Sponsor:

University of Calgary

Code:

NCT03356353

Conditions

End Stage Heart Failure

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Sildenafil Citrate

Study Details

Brief summary:

Continuous-flow left ventricular assist devices (LVAD) move blood from the left ventricle (the largest chamber of the heart) to the aorta (the body's main artery) to help the heart better meet the needs of the body and to improve survival for patients with advanced heart failure (HF). The ability of the right ventricle (the large chamber on the right side of the heart) to keep up with the improved blood flow following LVAD greatly effects how well a person does following surgery. It is understood that a high pulmonary artery pressure (pressure in the blood vessel that takes blood from the right side of the heart to the lungs) measured before surgery, indicates that a higher risk of right heart failure exists after LVAD implantation.

This is important because right heart failure after surgery is related to longer intensive care unit (ICU) and hospital stays, increased morbidity (other health problems) including organ failure and worse outcomes following heart transplant, and increased death rates.

Sildenafil (Revatio®) has been approved by Health Canada in the treatment of pulmonary arterial hypertension (high blood pressure in the lungs) in patients with connective tissue disease. Sildenafil has not yet been approved by Health Canada for the treatment of pulmonary hypertension in heart failure. Sildenafil lowers blood pressure in the lungs and lessens the workload of the right ventricle (the right side of the heart). The purpose of this study is to determine if lowering blood pressure in the lungs, in heart failure patients at risk for developing right heart failure after LVAD implant, lowers the incidence of right heart failure, shortens ICU and hospital stays and reduces morbidity (other health problems) and mortality (death rates).

This is an open label, single arm study. Everyone who participates in this study will receive sildenafil before and after LVAD surgery. It is expected that 24 patients who are scheduled to have LVAD implantation for advanced heart failure will be enrolled from 6 sites across Canada. Participants will be followed in the study for about 2 months.

Conditions

End Stage Heart Failure

Study ID

NCT03356353

Start date

Mar 12, 2018

Status verified date

Apr, 2021

Completion date

Jan, 2022

Anticipated

Primary completion date

Sep 30, 2021

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Patients aged >18 years who are to receive durable (HeartMate II or III, or HeartWare HVAD) LVAD implantation for end-stage HF. Patients with all etiologies of HF will be included.
  • Patients identified as having an increased risk for post-operative RHF using pre-operative hemodynamic assessment criteria, defined as the presence of ≥ 1 of the following: i) Central venous pressure (CVP):mean pulmonary capillary wedge pressure (PCWP) ratio ≥ 0.63 ii) RV stroke work index < 300 mmHg/mL/m2 iii) CVP ≥15 mmHg (CVP must be >8 mmHg if applying one of the other criteria) iv) Pre-operative PVR ≥ 3 Wood Units (240 dynes/cm5/sec)
  • Systolic blood pressure ≥ 85 mmHg at study initiation
  • Women of childbearing potential must have a negative pregnancy test. Women must not be breast feeding. Heterosexually active women of child bearing potential must use an effective method of contraception during the study.
  • Ability to sign informed consent to participate

Exclusion Criteria:

  • Preoperative INTERMACS level I or II
  • Preoperative systemic hypotension with mean arterial pressure < 60 mmHg
  • Planned insertion of RV support device (either temporary or permanent)
  • Complex congenital heart disease where PVR measurement is not feasible or reliable (repaired or unrepaired)
  • Right sided fixed or dynamic obstruction to blood flow (i.e., pulmonary stenosis) with resting gradient ≥ 10 mmHg.
  • Previous organ transplantation
  • Preoperative use of any oral pulmonary vasodilator therapy or oral/inhaled/nitrate therapy
  • Patients requiring pre-operative hem - or peritoneal dialysis
  • Pre-enrollment treatment with other pulmonary dilating agents such as other PDE5 inhibitors, endothelin antagonists, prostacyclin analogues. Use of postoperative nitric oxide will be permitted (although not concomitantly with the study medication) as clinically indicated in the postoperative setting
  • Lack of ability to invasively measure right-sided pulmonary pressures
  • Refusal or inability to sign informed consent
  • Inability to accept preoperative study drug, or known sensitivity or allergy to sildenafil or any of its ingredients, or any other contra-indication to sildenafil as identified by product monograph
  • Participation in any other current interventional (drug or device) study

Study Design

Enrollment

24 participants

Anticipated

Intervention Model

Single group

Primary purpose

Prevention

Interventions and Outcome Measures

Arms

experimental: sildenafil citrate

Following enrolment, participants will be given an initial dose of sildenafil 20 mg. If tolerated, a schedule of 20 mg three times daily (tid) will be initiated. Dosage will be titrated over 3-4 days to the target dose of 40 mg tid. If the initial dose is not tolerated, the participant will be exited from the trial.

Interventions

Sildenafil Citrate

20 mg tablets

Primary outcome measure

  • Pulmonary vascular resistance (PVR) [ Time Frame: From baseline to postoperative day 14 ]

Central Contacts and Locations

Central contacts

Nowell Fine, FRCPC

403-956-3748nowell.fine@albertahealthservices.ca

Jonathan Howlett, FRCPC

403-944-3232howlettjonathan@gmail.com

Locations

University of Calgary

Recruiting

Calgary, Alberta, Canada

Contacts

Nowell Fine, FRCPC

403.956.3748nowell.fine@albertahealthservices.ca

Leslie Jackson

403.220.8709jacksola@ucalgary.ca

St. Boniface Hospital

Recruiting

Winnipeg, Manitoba, Canada, R2H 2A6

Contacts

Wendy Janz

204.237.2793wjanz@hsc.mb.ca

London Health Sciences Centre

Recruiting

London, Ontario, Canada, N6A 5A5

Contacts

Heather Hern

519.685.8500Heather.Hern@lhsc.on.ca

University of Ottawa Heart Institute

Recruiting

Ottawa, Ontario, Canada, K1Y 4W7

Contacts

Allyson Thomas

613.696.7000athomas@ottawaheart.ca

Laura Menchini

613.696.7000lmenchini@ottawaheart.ca

More Information

Sponsor

University of Calgary

Last update posted

Apr 29, 2021

Last verified

Apr, 2021

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Calgary on 2021-04-29.