Heart Transplant SurgeryPhase 4INSPIRE-FLONCT03081052

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

A Phase 4 study testing iNO and iEPO in people with Heart Transplant Surgery and Lung Transplant Surgery, run by Duke University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Heart Transplant Surgery, Lung Transplant Surgery
What is being tested?: iNO and iEPO
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 519 participants
Where: 1 siteUnited States
Study dates: 4 May 2017to 5 Sep 2021
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Heart transplantation
LVAD placement
Lung Transplantation

Who cannot join

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

Show all 16Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Duke Health
Durham, North Carolina, 27710

Other trials in United States

About this study

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.

Read the 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.

Conditions: Heart Transplant Surgery, Lung Transplant Surgery
Being tested: iNO, iEPO
Keywords: Heart and Lung transplantation surgery, Pulmonary vasodilation therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

iNODrug
Also called Inhaled Nitric Oxide
Subject will receive inhaled Nitric Oxide in this intervention
iEPODrug
Also called Inhaled Epoprostrenol
Subject will receive inhaled Epoprostrenol in this intervention

Study groups in NCT03081052
Study group	Role	What they receive
Lung transplant with iNO	Active comparator	Not described Receives: Drug: iNO
Lung transplant with iEPO	Active comparator	Not described Receives: Drug: iEPO
Heart transplant & LVAD implantation with iNO	Active comparator	Not described Receives: Drug: iNO
Heart transplant & LVAD implantation with iEPO	Active comparator	Not described Receives: Drug: iEPO

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: up to approximately 21 days after LVAD placement, up to approximately 30 days after heart transplantation

Secondary outcomes (8)

Duration of Postoperative Mechanical Ventilation
Length of time from intubation until patient is extubated
Measured: 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.
Measured: up to approximately 30 days after index surgery
Length of ICU Stay
Length of time from ICU admission from surgery until ICU discharge
Measured: up to approximately 90 days after index surgery
Length of Hospital Stay
Length of time from surgery to hospital discharge
Measured: up to approximately 1 year after index surgery
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
Measured: up to approximately 14 days
Number of Participants With In-hospital Mortality
Death that occurs during the hospital stay
Measured: up to approximately 1 year after index surgery
Number of Participants With Post-operative Mortality Within 30 Days
From the day of surgery to 30 days postoperatively.
Measured: up to approximately 30 days after index surgery
Number of Participants With Post-operative Mortality Within 90 Days
From the day of surgery to 90 days after index surgery
Measured: up to approximately 90 days after index surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 May 20175 Sep 2021

First posted15 Mar 2017
Study start4 May 2017
Primary completion5 Oct 2020
Study completion5 Sep 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Heart Transplant SurgeryStudies of the same condition, open and under way.
More trials run by Duke UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 519 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03081052
Sponsor's protocol ID: Pro00078035
Acronym: INSPIRE-FLO
Status last verified: Feb 2023
First submitted: 8 Mar 2017
Last updated: 16 Feb 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Ghadimi K, Cappiello JL, Wright MC, Levy JH, Bryner BS, DeVore AD, Schroder JN, Patel CB, Rajagopal S, Shah SH, Milano CA; INSPIRE-FLO Investigators. Inhaled Epoprostenol Compared With Nitric Oxide for Right Ventricular Support After Major Cardiac Surgery. Circulation. 2023 Oct 24;148(17):1316-1329. doi: 10.1161/CIRCULATIONAHA.122.062464. Epub 2023 Jul 4.
PubMed 37401479
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.
PubMed 34787647

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Coronary Artery Bypass Graft (CABG)
Recruiting
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Coronary Artery Disease With Need for Bypass Surgery, Coronary Artery Disease(CAD)
Active, not recruitingPhase 1
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Intra and Post Operative Pain Management, Fast Track Program,(Enhanced Recovery After Surgery (ERAS))

All Heart Transplant Surgery trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Inhaled Selective Pulmonary Vasodilators for Advanced Heart Failure Therapies and Lung Transplantation Outcomes
ClinicalTrials.gov ID: NCT03081052
Acronym / sponsor ID: INSPIRE-FLO / Pro00078035
Conditions: Heart Transplant Surgery, Lung Transplant Surgery
Keywords: Heart and Lung transplantation surgery, Pulmonary vasodilation therapy
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 519 participants (actual)
Lead sponsor: Duke UniversityUniversity, hospital or other
Study start: 4 May 2017 (actual)
Primary completion: 5 Oct 2020 (actual)
Study completion: 5 Sep 2021 (actual)
First posted: 15 Mar 2017 (actual)
Results: Posted 10 Mar 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 4

Arm	Type	Receives
Lung transplant with iNO	Active comparator	Drug: iNO
Lung transplant with iEPO	Active comparator	Drug: iEPO
Heart transplant & LVAD implantation with iNO	Active comparator	Drug: iNO
Heart transplant & LVAD implantation with iEPO	Active comparator	Drug: iEPO

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Heart transplantation
LVAD placement
Lung Transplantation

Key exclusion criteria (16 listed)

Combined Organ Transplantation
Age < 18 years old
Pregnancy
Known allergy to prostaglandin (rare)
Refusal of blood products due to personal or religious preference

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
iNOAlso: Inhaled Nitric OxideSubject will receive inhaled Nitric Oxide in this intervention	Drug	Heart transplant & LVAD implantation with iNO, Lung transplant with iNO
iEPOAlso: Inhaled EpoprostrenolSubject will receive inhaled Epoprostrenol in this intervention	Drug	Heart transplant & LVAD implantation with iEPO, Lung transplant with iEPO

Primary outcome

Number of Participants With Grade 3 Primary Graft Dysfunction (PGD) for Lung Transplant Subjects
Time frame: 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.
Number of Participants With Moderate or Severe RV Failure for the LVAD Implantation Subjects and Severe RV Failure for Heart Transplantation Subjects
Time frame: 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.

8 secondary outcomes

Duration of Postoperative Mechanical Ventilation
Time frame: up to approximately 90 days after index surgery
Per Patient Inhaled Pulmonary Vasodilator (iPVD) Cost
Time frame: up to approximately 30 days after index surgery
Length of ICU Stay
Time frame: up to approximately 90 days after index surgery
Length of Hospital Stay
Time frame: up to approximately 1 year after index surgery
Number of Participants With Acute Kidney Injury
Time frame: up to approximately 14 days
Number of Participants With In-hospital Mortality
Time frame: up to approximately 1 year after index surgery
Number of Participants With Post-operative Mortality Within 30 Days
Time frame: up to approximately 30 days after index surgery
Number of Participants With Post-operative Mortality Within 90 Days
Time frame: up to approximately 90 days after index surgery

Results and safety

Results posted to the registry on 10 Mar 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lung Transplant With iNO	98	98
Lung Transplant With iEPO	103	103
Heart Transplant & LVAD Implantation With iNO	111	111
Heart Transplant & LVAD Implantation With iEPO	120	120

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

Time frame: Up to 72 hours. Count of participants. Unit: Participants

Measure	Lung Transplant With iNO n = 98	Lung Transplant With iEPO n = 103
Value	39	46

Lung Transplant With iNO vs Lung Transplant With iEPO: Risk Difference (RD): 0.049 (90% CI -0.064 to 0.162), p = 0.019, two one sided test p-value

Population analysed: Only applicable to lung transplant patients on protocol.

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

Time frame: up to approximately 21 days after LVAD placement, up to approximately 30 days after heart transplantation. Count of participants. Unit: Participants

Measure	Heart Transplant & LVAD Implantation With iNO n = 111	Heart Transplant & LVAD Implantation With iEPO n = 120
Value	25	30

Heart Transplant & LVAD Implantation With iNO vs Heart Transplant & LVAD Implantation With iEPO: Risk Difference (RD): 0.025 (90% CI -0.066 to 0.116), p = 0.012, two one-sided test p-value

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

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Collected from surgery to one year.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lung Transplant With iNO	9 of 98 (9.2%)	42 of 98 (42.9%)	9 of 98
Lung Transplant With iEPO	10 of 103 (9.7%)	41 of 103 (39.8%)	10 of 103
Heart Transplant & LVAD Implantation With iNO	10 of 111 (9%)	40 of 111 (36%)	10 of 111
Heart Transplant & LVAD Implantation With iEPO	21 of 120 (17.5%)	48 of 120 (40%)	21 of 120

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37401479Ghadimi K, Cappiello JL, Wright MC, Levy JH, Bryner BS, DeVore AD, Schroder JN, Patel CB, Rajagopal S, Shah SH, Milano CA; INSPIRE-FLO Investigators. Inhaled Epoprostenol Compared With Nitric Oxide for Right Ventricular Support After Major Cardiac Surgery. Circulation. 2023 Oct 24;148(17):1316-1329. doi: 10.1161/CIRCULATIONAHA.122.062464. Epub 2023 Jul 4.
Derived from this study: PubMed 34787647Ghadimi 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.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kamrouz Ghadimi, MD principal investigator

Duke Health

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing iNO and iEPO in people with Heart Transplant Surgery and Lung Transplant Surgery, run by Duke University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Grade 3 Primary Graft Dysfunction (PGD) for Lung Transplant Subjects (time frame: Up to 72 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03081052, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2023.