Inhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies and Lung Transplantation Outcomes

Duke University519 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

OTHER

Masking

TRIPLE

Enrollment

519

Conditions

Heart Transplant Surgery Lung Transplant Surgery

Interventions

iNODRUG

Subject will receive inhaled Nitric Oxide in this intervention

iEPODRUG

Subject will receive inhaled Epoprostrenol in this intervention

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Duke Health

Durham, North Carolina, United States

Outcomes

Primary Outcomes

Number of Participants With Grade 3 Primary Graft Dysfunction (PGD) for Lung Transplant Subjects

This is defined by the International Society of Heart and Lung Transplantation (ISHLT) as severe hypoxemia with a PaO2-to-FiO2 ratio \< 200 or the presence of venovenous extracorporeal membrane oxygenation (VV ECMO) at a time-point within the first 72 hours after lung transplantation.

Time frame: Up to 72 hours

Number of Participants With Moderate or Severe RV Failure for the LVAD Implantation Subjects and Severe RV Failure for Heart Transplantation Subjects

This is defined by the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) score of moderate or severe right-heart failure for LVADS, and by the incidence of an RVAD placement or ECMO for RHF for heart transplants.

Time frame: up to approximately 21 days after LVAD placement, up to approximately 30 days after heart transplantation

Secondary Outcomes

Duration of Postoperative Mechanical Ventilation

Length of time from intubation until patient is extubated

Time frame: up to approximately 90 days after index surgery

Per Patient Inhaled Pulmonary Vasodilator (iPVD) Cost

Data reflects a per patient cost in dollars that has been scaled to a unit of measure relative to the cost per hour of drug and multiplied by the duration of iPVD administration. In our study, iNO cost 7 times that of iEPO per hour, hence for each patient this outcome value is the duration of iPVD administration multiplied by 7 if a patient is randomized to iNO or multiplied by 1 if randomized to iEPO.

Time frame: up to approximately 30 days after index surgery

Length of ICU Stay

Length of time from ICU admission from surgery until ICU discharge

Time frame: up to approximately 90 days after index surgery

Data from ClinicalTrials.gov

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