Back to resultsInhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies and Lung Transplantation Outcomes (INSPIRE-FLO)
Primary Purpose
Heart Transplant Surgery, Lung Transplant Surgery
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
iNO
iEPO
Sponsored by
About this trial
This is an interventional other trial for Heart Transplant Surgery focused on measuring Heart and Lung transplantation surgery, Pulmonary vasodilation therapy
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
Sites / Locations
- Duke Health
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
Lung transplant with iNO
Lung transplant with iEPO
Heart transplant & LVAD implantation with iNO
Heart transplant & LVAD implantation with iEPO
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Duration of Postoperative Mechanical Ventilation
Length of time from intubation until patient is extubated
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.
Length of ICU Stay
Length of time from ICU admission from surgery until ICU discharge
Length of Hospital Stay
Length of time from surgery to hospital discharge
Number of Participants With Acute Kidney Injury
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 In-hospital Mortality
Death that occurs during the hospital stay
Number of Participants With Post-operative Mortality Within 30 Days
From the day of surgery to 30 days postoperatively.
Number of Participants With Post-operative Mortality Within 90 Days
From the day of surgery to 90 days after index surgery
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03081052
Brief Title
Inhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies and Lung Transplantation Outcomes
Acronym
INSPIRE-FLO
Official Title
Inhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies and Lung Transplantation Outcomes
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
May 4, 2017 (Actual)
Primary Completion Date
October 5, 2020 (Actual)
Study Completion Date
September 5, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Transplant Surgery, Lung Transplant Surgery
Keywords
Heart and Lung transplantation surgery, Pulmonary vasodilation therapy
7. Study Design
Primary Purpose
Other
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
519 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Lung transplant with iNO
Arm Type
Active Comparator
Arm Title
Lung transplant with iEPO
Arm Type
Active Comparator
Arm Title
Heart transplant & LVAD implantation with iNO
Arm Type
Active Comparator
Arm Title
Heart transplant & LVAD implantation with iEPO
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
iNO
Other Intervention Name(s)
Inhaled Nitric Oxide
Intervention Description
Subject will receive inhaled Nitric Oxide in this intervention
Intervention Type
Drug
Intervention Name(s)
iEPO
Other Intervention Name(s)
Inhaled Epoprostrenol
Intervention Description
Subject will receive inhaled Epoprostrenol in this intervention
Primary Outcome Measure Information:
Title
Number of Participants With Grade 3 Primary Graft Dysfunction (PGD) for Lung Transplant Subjects
Description
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
Title
Number of Participants With Moderate or Severe RV Failure for the LVAD Implantation Subjects and Severe RV Failure for Heart Transplantation Subjects
Description
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 Outcome Measure Information:
Title
Duration of Postoperative Mechanical Ventilation
Description
Length of time from intubation until patient is extubated
Time Frame
up to approximately 90 days after index surgery
Title
Per Patient Inhaled Pulmonary Vasodilator (iPVD) Cost
Description
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
Title
Length of ICU Stay
Description
Length of time from ICU admission from surgery until ICU discharge
Time Frame
up to approximately 90 days after index surgery
Title
Length of Hospital Stay
Description
Length of time from surgery to hospital discharge
Time Frame
up to approximately 1 year after index surgery
Title
Number of Participants With Acute Kidney Injury
Description
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
Time Frame
up to approximately 14 days
Title
Number of Participants With In-hospital Mortality
Description
Death that occurs during the hospital stay
Time Frame
up to approximately 1 year after index surgery
Title
Number of Participants With Post-operative Mortality Within 30 Days
Description
From the day of surgery to 30 days postoperatively.
Time Frame
up to approximately 30 days after index surgery
Title
Number of Participants With Post-operative Mortality Within 90 Days
Description
From the day of surgery to 90 days after index surgery
Time Frame
up to approximately 90 days after index surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kamrouz Ghadimi, MD
Organizational Affiliation
Duke Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke Health
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34787647
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.
Results Reference
derived
Learn more about this trial
Inhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies and Lung Transplantation Outcomes
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