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

Phase 4

Completed

Conditions: Lung Transplant Surgery
Heart Transplant Surgery

Interventions: Drug: iEPO
Drug: iNO

Registration Number: NCT03081052

Lead Sponsor: Duke University

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 519

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Heart transplant & LVAD implantation with iEPO	iEPO	-
Lung transplant with iNO	iNO	-
Lung transplant with iEPO	iEPO	-
Heart transplant & LVAD implantation with iNO	iNO	-

Primary Outcome Measures

Name	Time	Method
Number of Participants With Moderate or Severe RV Failure for the LVAD Implantation Subjects and Severe RV Failure for Heart Transplantation Subjects	up to approximately 21 days after LVAD placement, up to approximately 30 days after heart transplantation	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.
Number of Participants With Grade 3 Primary Graft Dysfunction (PGD) for Lung Transplant Subjects	Up to 72 hours	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.

Secondary Outcome Measures

Name	Time	Method
Length of ICU Stay	up to approximately 90 days after index surgery	Length of time from ICU admission from surgery until ICU discharge
Duration of Postoperative Mechanical Ventilation	up to approximately 90 days after index surgery	Length of time from intubation until patient is extubated
Per Patient Inhaled Pulmonary Vasodilator (iPVD) Cost	up to approximately 30 days after index surgery	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.
Number of Participants With Acute Kidney Injury	up to approximately 14 days	defined by Modified KDIGO-AKI definition: * Increase in Serum Creatinine (Cr) by ≥0.3mg/dL within 48 hours; or * Increase in Cr to ≥1.5 times baseline * Urine output is not included as urine could be under-captured after Foley catheter removal
Number of Participants With Post-operative Mortality Within 30 Days	up to approximately 30 days after index surgery	From the day of surgery to 30 days postoperatively.
Length of Hospital Stay	up to approximately 1 year after index surgery	Length of time from surgery to hospital discharge
Number of Participants With In-hospital Mortality	up to approximately 1 year after index surgery	Death that occurs during the hospital stay
Number of Participants With Post-operative Mortality Within 90 Days	up to approximately 90 days after index surgery	From the day of surgery to 90 days after index surgery