INSPIRE-FLO: Inhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies and Lung Transplantation Outcomes

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03081052
• Collaborator: (none)
• Enrollment: 519
• Location: 1
• Arms: 4
• Actual Duration (Months): 52.1
• Patients Per Site Per Month: 10

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Transplant Surgery; Lung Transplant Surgery	Drug: iNO; Drug: iEPO	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 519 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Other
• Official Title: Inhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies and Lung Transplantation Outcomes
• Actual Study Start Date: May 4, 2017
• Actual Primary Completion Date: Oct 5, 2020
• Actual Study Completion Date: Sep 5, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lung transplant with iNO	Drug: iNO; Subject will receive inhaled Nitric Oxide in this intervention; Other Names: Inhaled Nitric Oxide
Active Comparator: Lung transplant with iEPO	Drug: iEPO; Subject will receive inhaled Epoprostrenol in this intervention; Other Names: Inhaled Epoprostrenol
Active Comparator: Heart transplant & LVAD implantation with iNO	Drug: iNO; Subject will receive inhaled Nitric Oxide in this intervention; Other Names: Inhaled Nitric Oxide
Active Comparator: Heart transplant & LVAD implantation with iEPO	Drug: iEPO; Subject will receive inhaled Epoprostrenol in this intervention; Other Names: Inhaled Epoprostrenol

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

Secondary Outcome Measures

1. Duration of Postoperative Mechanical Ventilation [up to approximately 90 days after index surgery]

   Length of time from intubation until patient is extubated

2. 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.

3. Length of ICU Stay [up to approximately 90 days after index surgery]

   Length of time from ICU admission from surgery until ICU discharge

4. Length of Hospital Stay [up to approximately 1 year after index surgery]

   Length of time from surgery to hospital discharge

5. 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

6. Number of Participants With In-hospital Mortality [up to approximately 1 year after index surgery]

   Death that occurs during the hospital stay

7. 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.

8. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke Health	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University

Investigators

• Principal Investigator: Kamrouz Ghadimi, MD, Duke Health

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 26, 2018

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03081052
• Other Study ID Numbers: Pro00078035
• First Posted: Mar 15, 2017
• Last Update Posted: Mar 10, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Duke University: Heart and Lung transplantation surgery; Pulmonary vasodilation therapy
• Additional relevant MeSH terms: Heart Failure; Nitric Oxide

Study Results

Participant Flow

Pre-assignment Detail	519 participants were randomized, but 87 of those were unable to undergo surgery on protocol. 432 participants started the study (i.e., underwent surgery on protocol).

Arm/Group Title	Lung Transplant With iNO	Lung Transplant With iEPO	Heart Transplant & LVAD Implantation With iNO	Heart Transplant & LVAD Implantation With iEPO
Arm/Group Description	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention
Period Title: Overall Study
STARTED	98	103	111	120
COMPLETED	98	103	111	120
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Lung Transplant With iNO	Lung Transplant With iEPO	Heart Transplant & LVAD Implantation With iNO	Heart Transplant & LVAD Implantation With iEPO	Total
Arm/Group Description	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention	Total of all reporting groups
Overall Participants	98	103	111	120	432
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	64	64	59	58	60
Sex: Female, Male (Count of Participants)
Female	39 39.8%	33 32%	25 22.5%	35 29.2%	132 30.6%
Male	59 60.2%	70 68%	86 77.5%	85 70.8%	300 69.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 2%	3 2.9%	3 2.7%	1 0.8%	9 2.1%
Not Hispanic or Latino	92 93.9%	96 93.2%	107 96.4%	116 96.7%	411 95.1%
Unknown or Not Reported	4 4.1%	4 3.9%	1 0.9%	3 2.5%	12 2.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1%	0 0%	0 0%	0 0%	1 0.2%
Asian	0 0%	1 1%	0 0%	0 0%	1 0.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	12 12.2%	9 8.7%	44 39.6%	47 39.2%	112 25.9%
White	83 84.7%	91 88.3%	66 59.5%	72 60%	312 72.2%
More than one race	1 1%	0 0%	0 0%	1 0.8%	2 0.5%
Unknown or Not Reported	1 1%	2 1.9%	1 0.9%	0 0%	4 0.9%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Only applicable to lung transplant patients on protocol.

Arm/Group Title	Lung Transplant With iNO	Lung Transplant With iEPO
Arm/Group Description	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention
Measure Participants	98	103
Count of Participants [Participants]	39 39.8%	46 44.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lung Transplant With iNO, Lung Transplant With iEPO
	Comments
	Type of Statistical Test	Equivalence
	Comments	We estimated sample size based on equivalence test of the incidence rates of a binary outcome (e.g. PGD grade 3 (PGD-3)) of two treatment groups as an illustration. Assuming the incidence rate of PGD-3 under iEPO treatment is 0.30 and acceptable margin of the equivalence is ± 0.19, we will need 200 lung transplant patients to have 80% power to detect an actual difference at α=0.05 between two treatment group under this margin.
Statistical Test of Hypothesis	p-Value	0.019
	Comments
	Method	two one sided test p-value
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.049
	Confidence Interval	(2-Sided) 90%; -0.064 to 0.162
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Only applicable to heart transplant and LVAD implantation cohort that were treated on protocol.

Arm/Group Title	Heart Transplant & LVAD Implantation With iNO	Heart Transplant & LVAD Implantation With iEPO
Arm/Group Description	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention
Measure Participants	111	120
Count of Participants [Participants]	25 25.5%	30 29.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lung Transplant With iNO, Lung Transplant With iEPO
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	We estimated sample size based on equivalence test of the incidence rates of a binary outcome of two treatment groups as an illustration. Assuming the incidence rate of moderate or severe RV failure under iEPO treatment is 0.113 and acceptable margin of the equivalence is ± 0.15, we will need 224 heart failure patients to have 80% power to detect an actual difference at α=0.05 between two treatment group under this margin.
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	two one-sided test p-value
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.025
	Confidence Interval	(2-Sided) 90%; -0.066 to 0.116
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Among patients extubated, if patients transitioned directly from intubation to tracheostomy the duration of mechanical ventilation was censored at the time of tracheostomy placement

Arm/Group Title	Lung Transplant With iNO	Lung Transplant With iEPO	Heart Transplant & LVAD Implantation With iNO	Heart Transplant & LVAD Implantation With iEPO
Arm/Group Description	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention	iNO: Subjects will receive inhaled Nitric Oxide in this intervention	iEPO: Subjects will receive inhaled Epoprostrenol in this intervention
Measure Participants	97	100	111	119
Median (Inter-Quartile Range) [hours]	17	18	26	24

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lung Transplant With iNO, Lung Transplant With iEPO
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.747
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann Location Shift
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; -3 to 3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Heart Transplant & LVAD Implantation With iNO, Heart Transplant & LVAD Implantation With iEPO
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.638
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hodges-Lehmann Location Shift
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; -1 to 1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lung Transplant With iNO	Lung Transplant With iEPO	Heart Transplant & LVAD Implantation With iNO	Heart Transplant & LVAD Implantation With iEPO
Arm/Group Description	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention
Measure Participants	98	103	111	120
Mean (Standard Deviation) [relative cost units]	544 (513)	70 (70)	772 (554)	114 (121)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lung Transplant With iNO	Lung Transplant With iEPO	Heart Transplant & LVAD Implantation With iNO	Heart Transplant & LVAD Implantation With iEPO
Arm/Group Description	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention	iNO: Subjects will receive inhaled Nitric Oxide in this intervention	iEPO: Subjects will receive inhaled Epoprostrenol in this intervention
Measure Participants	98	103	111	120
Median (Inter-Quartile Range) [days]	4	4	6	6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lung Transplant With iNO, Lung Transplant With iEPO
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.453
	Comments
	Method	log-linear regression
	Comments
Method of Estimation	Estimation Parameter	mean ratio
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.76 to 1.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Heart Transplant & LVAD Implantation With iNO, Heart Transplant & LVAD Implantation With iEPO
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.816
	Comments
	Method	log-linear regression
	Comments
Method of Estimation	Estimation Parameter	mean ratio
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.57 to 1.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Length of Hospital Stay
Description	Length of time from surgery to hospital discharge
Time Frame	up to approximately 1 year after index surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lung Transplant With iNO	Lung Transplant With iEPO	Heart Transplant & LVAD Implantation With iNO	Heart Transplant & LVAD Implantation With iEPO
Arm/Group Description	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention	iNO: Subjects will receive inhaled Nitric Oxide in this intervention	iEPO: Subjects will receive inhaled Epoprostrenol in this intervention
Measure Participants	98	103	111	120
Median (Inter-Quartile Range) [days]	23	23	16	17

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lung Transplant With iNO, Lung Transplant With iEPO
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.864
	Comments
	Method	log-linear regression
	Comments
Method of Estimation	Estimation Parameter	mean ratio
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Heart Transplant & LVAD Implantation With iNO, Heart Transplant & LVAD Implantation With iEPO
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.825
	Comments
	Method	log-linear regression
	Comments
Method of Estimation	Estimation Parameter	mean ratio
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lung Transplant With iNO	Lung Transplant With iEPO	Heart Transplant & LVAD Implantation With iNO	Heart Transplant & LVAD Implantation With iEPO
Arm/Group Description	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention
Measure Participants	98	103	111	120
Count of Participants [Participants]	72 73.5%	68 66%	96 86.5%	101 84.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lung Transplant With iNO, Lung Transplant With iEPO
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.251
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95%; 0.78 to 2.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Heart Transplant & LVAD Implantation With iNO, Heart Transplant & LVAD Implantation With iEPO
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.619
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; 0.58 to 2.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lung Transplant With iNO	Lung Transplant With iEPO	Heart Transplant & LVAD Implantation With iNO	Heart Transplant & LVAD Implantation With iEPO
Arm/Group Description	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention	iNO: Subjects will receive inhaled Nitric Oxide in this intervention	iEPO: Subjects will receive inhaled Epoprostrenol in this intervention
Measure Participants	98	103	111	120
Count of Participants [Participants]	5 5.1%	7 6.8%	6 5.4%	11 9.2%

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lung Transplant With iNO	Lung Transplant With iEPO	Heart Transplant & LVAD Implantation With iNO	Heart Transplant & LVAD Implantation With iEPO
Arm/Group Description	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention
Measure Participants	98	103	111	120
Count of Participants [Participants]	2 2%	1 1%	4 3.6%	7 5.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lung Transplant With iNO, Lung Transplant With iEPO
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.614
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.13
	Confidence Interval	(2-Sided) 95%; 0.19 to 23.82
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Heart Transplant & LVAD Implantation With iNO, Heart Transplant & LVAD Implantation With iEPO
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5424
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; 0.17 to 2.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lung Transplant With iNO	Lung Transplant With iEPO	Heart Transplant & LVAD Implantation With iNO	Heart Transplant & LVAD Implantation With iEPO
Arm/Group Description	iNO: Subject will receive inhaled Nitric Oxide in this intervention	iEPO: Subject will receive inhaled Epoprostrenol in this intervention	iNO: Subjects will receive inhaled Nitric Oxide in this intervention	iEPO: Subjects will receive inhaled Epoprostrenol in this intervention
Measure Participants	98	103	111	120
Count of Participants [Participants]	4 4.1%	4 3.9%	5 4.5%	12 10%

Adverse Events

Time Frame	Collected from surgery to one year.
Adverse Event Reporting Description	Patients who were consented and randomized, but excluded or withdrawn prior to surgery and treatment are not included in this cohort description. No participant data was retained after patient exclusion or withdrawal prior to surgery and treatment. Due to the nature of the study design, comparative trial evaluating two standard of care medications, the only SAE reported is mortality at specified intervals.
Arm/Group Title	Lung Transplant With iNO		Lung Transplant With iEPO		Heart Transplant & LVAD Implantation With iNO		Heart Transplant & LVAD Implantation With iEPO
Arm/Group Description	iNO: Subject will receive inhaled Nitric Oxide in this intervention		iEPO: Subject will receive inhaled Epoprostrenol in this intervention		iNO: Subject will receive inhaled Nitric Oxide in this intervention		iEPO: Subject will receive inhaled Epoprostrenol in this intervention
All Cause Mortality
	Lung Transplant With iNO		Lung Transplant With iEPO		Heart Transplant & LVAD Implantation With iNO		Heart Transplant & LVAD Implantation With iEPO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/98 (9.2%)		10/103 (9.7%)		10/111 (9%)		21/120 (17.5%)
Serious Adverse Events
	Lung Transplant With iNO		Lung Transplant With iEPO		Heart Transplant & LVAD Implantation With iNO		Heart Transplant & LVAD Implantation With iEPO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/98 (9.2%)		10/103 (9.7%)		10/111 (9%)		21/120 (17.5%)
General disorders
All Cause Mortality	9/98 (9.2%)	9	10/103 (9.7%)	10	10/111 (9%)	10	21/120 (17.5%)	21
Other (Not Including Serious) Adverse Events
	Lung Transplant With iNO		Lung Transplant With iEPO		Heart Transplant & LVAD Implantation With iNO		Heart Transplant & LVAD Implantation With iEPO
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/98 (42.9%)		41/103 (39.8%)		40/111 (36%)		48/120 (40%)
Blood and lymphatic system disorders
Venous Thromboemolic DVT	27/98 (27.6%)	27	21/103 (20.4%)	21	21/111 (18.9%)	21	28/120 (23.3%)	28
Venous Thromboembolic PE	5/98 (5.1%)	5	10/103 (9.7%)	10	4/111 (3.6%)	4	4/120 (3.3%)	4
Venous Thromboembolic Other	13/98 (13.3%)	13	10/103 (9.7%)	10	8/111 (7.2%)	8	17/120 (14.2%)	17
Arterial Thromboembolic TIA	0/98 (0%)	0	2/103 (1.9%)	2	1/111 (0.9%)	1	1/120 (0.8%)	1
Arterial Thromboembolic CVA/Stroke	6/98 (6.1%)	6	2/103 (1.9%)	2	7/111 (6.3%)	7	8/120 (6.7%)	8
Arterial Thromboembolic Myocardial Infarction	2/98 (2%)	2	4/103 (3.9%)	4	1/111 (0.9%)	1	0/120 (0%)	0
Arterial Thromboembolic Mesenteric Ischemia	3/98 (3.1%)	3	2/103 (1.9%)	2	2/111 (1.8%)	2	4/120 (3.3%)	4
Arterial Thromboembolic Other	0/98 (0%)	0	2/103 (1.9%)	2	3/111 (2.7%)	3	3/120 (2.5%)	3
LVAD Thrombosis	0/98 (0%)	0	0/103 (0%)	0	1/111 (0.9%)	1	1/120 (0.8%)	1
Cardiac disorders
New Onset Atrial Fibrillation	11/98 (11.2%)	11	18/103 (17.5%)	18	10/111 (9%)	10	9/120 (7.5%)	9
Gastrointestinal disorders
Upper GI Bleed	2/98 (2%)	2	5/103 (4.9%)	5	4/111 (3.6%)	4	6/120 (5%)	6
Lower GI Bleed	1/98 (1%)	1	4/103 (3.9%)	4	2/111 (1.8%)	2	6/120 (5%)	6
Intestinal Perforation	0/98 (0%)	0	3/103 (2.9%)	3	1/111 (0.9%)	1	2/120 (1.7%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.