Clinical trial NCT03081052: Inhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies and Lung Transplantation Outcomes
Official title: Inhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies and Lung Transplantation Outcomes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Heart Transplant Surgery
Lung Transplant Surgery
Keywords: Heart and Lung transplantation surgery
Pulmonary vasodilation therapy
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2017-03-15
Enrollment: 519
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 1. to conduct a clinical investigation to determine if inhaled epoprostenol (Veletri®, iEPO) and inhaled nitric oxide (iNO) will have similar impact on outcomes in adult patients undergoing durable LVAD placement, heart transplantation, or lung transplantation 2. to conduct a cost-capture analysis on the expense each drug incurs per patient.

Detailed description: In adult cardiothoracic surgical patients, iNO is used to treat precapillary pulmonary hypertension (PH), right-sided heart failure (RHF), and ventilation-to-perfusion (V:Q) mismatch. Adult patients who undergo durable LVAD implantation (e.g. Heartware®, Heartmate 2®, or Heartmate 3®), cardiac transplantation for HFrEF, or those that have endured lung transplantation as a result of end-stage lung disease, compose the largest subpopulation which receives iPVD therapy at Duke University Hospital. iEPO may display an equivalent efficacy profile to iNO for pulmonary vasodilation and oxygenation and have a similar impact on clinical outcomes.

Subjects undergoing LVAD placement or heart transplantation (N=224) or lung transplantation (N=200) will be prospectively enrolled over a three-year period (one-year for follow-up). Patients will be randomly assigned 1:1 according to stratified randomization blocking either iNO or iEPO. Additional study procedures will involve data collection, blood, and tissue sampling.

Eligibility criteria: Inclusion Criteria:

* Heart transplantation
* LVAD placement
* Lung Transplantation

Exclusion Criteria:

* Combined Organ Transplantation
* Age \< 18 years old
* Pregnancy
* Known allergy to prostaglandin (rare)
* Refusal of blood products due to personal or religious preference
* Subject is enrolled in another study protocol, which does not allow randomization of PVD therapy
* Heart transplant or durable LVAD recipients with adult congenital heart disease (CHD)

  o Caveat: Does NOT meet exclusion criteria if the scheduled heart transplant or LVAD implantation is due to heart failure from a previous heart transplantation related to CHD, performed more than 90 days previous to the date of trial enrollment
* Heart transplant recipients diagnosed with Arrythmogenic Right Ventricular Cardiomyopathy
* Heart transplant recipients diagnosed with Acute Cardiac Allograft Rejection after a previous heart transplantation.
* Heart transplant or durable LVAD recipients with preoperative RVAD for right heart failure
* Patient is scheduled to undergo lung transplantation but has undergone heart transplantation in the previous 90 days
* Patient is scheduled to undergo durable LVAD implantation but has undergone heart transplantation in the previous 90 days
* Patient is scheduled to undergo heart transplantation but has undergone lung transplantation in the previous 90 days
* Patients with preoperative Venovenous ECMO as a bridge to lung transplantation
* Heart transplant or durable LVAD recipients with preoperative RVAD for right heart failure

Primary outcomes:
measure: Number of Participants With Grade 3 Primary Graft Dysfunction (PGD) for Lung Transplant Subjects
timeFrame: Up to 72 hours
measure: Number of Participants With Moderate or Severe RV Failure for the LVAD Implantation Subjects and Severe RV Failure for Heart Transplantation Subjects
timeFrame: up to approximately 21 days after LVAD placement, up to approximately 30 days after heart transplantation
Secondary outcomes:
measure: Duration of Postoperative Mechanical Ventilation
timeFrame: up to approximately 90 days after index surgery
measure: Per Patient Inhaled Pulmonary Vasodilator (iPVD) Cost
timeFrame: up to approximately 30 days after index surgery
measure: Length of ICU Stay
timeFrame: up to approximately 90 days after index surgery
measure: Length of Hospital Stay
timeFrame: up to approximately 1 year after index surgery
measure: Number of Participants With Acute Kidney Injury
timeFrame: up to approximately 14 days
measure: Number of Participants With In-hospital Mortality
timeFrame: up to approximately 1 year after index surgery
measure: Number of Participants With Post-operative Mortality Within 30 Days
timeFrame: up to approximately 30 days after index surgery
measure: Number of Participants With Post-operative Mortality Within 90 Days
timeFrame: up to approximately 90 days after index surgery
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Health
state: North Carolina
Study officials:
affiliation: Duke Health
name: Kamrouz Ghadimi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ghadimi K, Cappiello J, Cooter-Wright M, Haney JC, Reynolds JM, Bottiger BA, Klapper JA, Levy JH, Hartwig MG; INSPIRE-FLO Investigators. Inhaled Pulmonary Vasodilator Therapy in Adult Lung Transplant: A Randomized Clinical Trial. JAMA Surg. 2022 Jan 1;157(1):e215856. doi: 10.1001/jamasurg.2021.5856. Epub 2022 Jan 12.