Sildenafil for the Prevention of Right Heart Failure Following LVAD Implantation

NCT03356353 | Unknown Phase 3

• 1 other identifier: RVD102017
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 4

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

Outcome Measures

Primary Outcomes (1)

• Pulmonary vascular resistance (PVR)

  Change in PVR reported in Wood Units as measured invasively via right heart catheterization (RHC)

  From baseline to postoperative day 14

Secondary Outcomes (6)

• Right heart failure (RHF)

  From baseline to day 55 (end of study)

• RHF

  Postoperative day 14 to postoperative day 55 (end of study)

• RHF

  From baseline to postoperative day 55 (end of study)

• Inotrope requirement

  From baseline to day 55 (study end)

• ICU

  From baseline to day 55 (end of study)

Other Outcomes (10)

• Safety: Drug interruptions

  From baseline to day 55 (study end)

• Safety: Renal

  From baseline to day 55 (study end)

• Safety: All-cause mortality

  From enrollment to day 85 (final SAE review)

Study Arms (1)

sildenafil citrate

EXPERIMENTAL

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.

Drug: Sildenafil Citrate

Interventions

Sildenafil Citrate DRUG

20 mg tablets

Also known as: Revatio

sildenafil citrate

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Calgary: lead
• Pfizer: collaborator

Study Sites (4)

University of Calgary

Calgary, Alberta, Canada

RECRUITING

St. Boniface Hospital

Winnipeg, Manitoba, R2H 2A6, Canada

RECRUITING

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

RECRUITING

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

RECRUITING

Related Publications (1)

• Fine NM, Litwin O, Kent WDT, Holloway DD, Roy J, Miller RJH, Chih S, Davey RA, Isaac DL, Sharma N, Lyons KJ, Howlett JG. Feasibility of Sildenafil for the Prevention of Right Heart Failure After Continuous-Flow Left Ventricular Assist Device Implantation: The REVAD Trial. Can J Cardiol. 2024 Apr;40(4):659-661. doi: 10.1016/j.cjca.2023.11.017. Epub 2023 Nov 22. No abstract available.

  PMID: 37995907 DERIVED

MeSH Terms

Interventions

Sildenafil Citrate

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

Study Officials

• Jonathan Howlett, FRCPC

  University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nowell Fine, FRCPC

CONTACT

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

Jonathan Howlett, FRCPC

CONTACT

403-944-3232; howlettjonathan@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an open label single arm trial.

Study Record Dates

• First Submitted: November 22, 2017
• First Posted: November 29, 2017
• Study Start: March 12, 2018
• Primary Completion: September 30, 2021
• Study Completion: January 1, 2022
• Last Updated: April 29, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)