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Sildenafil for the Prevention of Right Heart Failure Following LVAD Implantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03356353
Recruitment Status : Unknown
Verified April 2021 by University of Calgary.
Recruitment status was:  Recruiting
First Posted : November 29, 2017
Last Update Posted : April 29, 2021
Information provided by (Responsible Party):
University of Calgary

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.

Condition or disease Intervention/treatment Phase
End Stage Heart Failure Drug: Sildenafil Citrate Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is an open label single arm trial.
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Sildenafil for the Prevention of Right Heart Failure Following Continuous-Flow Left Ventricular Assist Device Implantation (The REVAD Study)
Actual Study Start Date : March 12, 2018
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
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.
Drug: Sildenafil Citrate
20 mg tablets
Other Name: Revatio

Primary Outcome Measures :
  1. Pulmonary vascular resistance (PVR) [ Time Frame: From baseline to postoperative day 14 ]
    Change in PVR reported in Wood Units as measured invasively via right heart catheterization (RHC)

Secondary Outcome Measures :
  1. Right heart failure (RHF) [ Time Frame: From baseline to day 55 (end of study) ]
    Proportion of participants experiencing RHF defined as INTERMACS criteria: i) Requirement of continuous-flow right ventricular assist device (RVAD) implantation for hemodynamic support any time prior to study end

  2. RHF [ Time Frame: Postoperative day 14 to postoperative day 55 (end of study) ]
    Proportion of participants experiencing RHF defined as INTERMACS criteria: ii) Prolonged inotropic support beyond postoperative day 14 directed for clinical RHF

  3. RHF [ Time Frame: From baseline to postoperative day 55 (end of study) ]
    Proportion of participants experiencing RHF defined as INTERMACS criteria: iii) Discontinuation of study drug for the purpose of introduction of additional pulmonary vasodilator for the purpose of treatment of clinical RHF at any time during the study protocol

  4. Inotrope requirement [ Time Frame: From baseline to day 55 (study end) ]
    Proportion of patients requiring any inotrope medication at study end

  5. ICU [ Time Frame: From baseline to day 55 (end of study) ]
    Total number of hours in ICU by study end

  6. Hospitalization [ Time Frame: From baseline to day 55 (end of study) ]
    Total hospital length of stay by study end

Other Outcome Measures:
  1. Safety: Drug interruptions [ Time Frame: From baseline to day 55 (study end) ]
    Proportion of patients with temporary or permanent study drug interruptions

  2. Safety: Renal [ Time Frame: From baseline to day 55 (study end) ]
    Proportion of patients requiring renal replacement therapy or doubling of serum creatinine

  3. Safety: All-cause mortality [ Time Frame: From enrollment to day 85 (final SAE review) ]
    All-cause mortality at study end

  4. Safety: Transfusion [ Time Frame: From baseline to hospital discharge ]
    Total number of units of packed red cells transfused during hospital stay

  5. Safety: GFR [ Time Frame: From baseline fo day 55 (study end) ]
    Greatest percentage increase in glomerular filtration rate from baseline at any time during study

  6. Safety: Mean arterial pressure [ Time Frame: At ICU discharge and at day 55 (study end) ]
    Mean arterial pressure

  7. Safety: Symptomatic hypotension [ Time Frame: From baseline to day 55 (study end) ]
    Proportion of patients with > or = 1 episodes of symptomatic hypotension (syncope or orthostatic hypotension)

  8. Safety: Liver enzymes [ Time Frame: From baseline to day 55 (study end) ]
    Increase in hepatic enzymes > or = 2x baseline (preoperative) levels

  9. Safety: Pump time [ Time Frame: LVAD implantation day ]
    Total cardiac surgical bypass pump time

  10. Safety: Adverse drug reactions [ Time Frame: From baseline to day 85 (final SAE review) ]
    Any and all adverse drug reactions

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03356353

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Contact: Nowell Fine, FRCPC 403-956-3748
Contact: Jonathan Howlett, FRCPC 403-944-3232

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Canada, Alberta
University of Calgary Recruiting
Calgary, Alberta, Canada
Contact: Nowell Fine, FRCPC    403.956.3748   
Contact: Leslie Jackson    403.220.8709   
Canada, Manitoba
St. Boniface Hospital Recruiting
Winnipeg, Manitoba, Canada, R2H 2A6
Contact: Wendy Janz    204.237.2793   
Canada, Ontario
London Health Sciences Centre Recruiting
London, Ontario, Canada, N6A 5A5
Contact: Ryan Davey, FRCPC         
Contact: Heather Hern    519.685.8500 ext 32818   
University of Ottawa Heart Institute Recruiting
Ottawa, Ontario, Canada, K1Y 4W7
Contact: Allyson Thomas    613.696.7000 ext 15011   
Contact: Laura Menchini    613.696.7000 ext 18089   
Sponsors and Collaborators
University of Calgary
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Principal Investigator: Jonathan Howlett, FRCPC University of Calgary
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Responsible Party: University of Calgary Identifier: NCT03356353    
Other Study ID Numbers: RVD102017
First Posted: November 29, 2017    Key Record Dates
Last Update Posted: April 29, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
Sildenafil Citrate
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Urological Agents