Trial Outcomes & Findings for Sodium Nitrite in Lung Transplant Patients to Minimize the Risk of Pulmonary Graft Dysfunction (NCT NCT01715883)

Results Overview

The safety of Sodium Nitrite administration will be assessed by methemoglobin levels during and 150 minutes after the nitrite infusion in the transplant recipient.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

150 minutes post infusion

Results posted on

2018-08-01

Participant Flow

Participant milestones

Participant milestones
Measure	Sodium Nitrite Sodium Nitrite will be administered at three time points: At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8 Liter bags of Perfadex solution to flush the donor lungs. At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the portal vein (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes. Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min. Sodium Nitrite: Same as the details in Arm Description.
Overall Study STARTED	3
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sodium Nitrite in Lung Transplant Patients to Minimize the Risk of Pulmonary Graft Dysfunction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sodium Nitrite n=3 Participants Sodium Nitrite will be administered at three time points: At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8 Liter bags of Perfadex solution to flush the donor lungs. At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the portal vein (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes. Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min. Sodium Nitrite: Same as the details in Arm Description.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 150 minutes post infusion

The safety of Sodium Nitrite administration will be assessed by methemoglobin levels during and 150 minutes after the nitrite infusion in the transplant recipient.

Outcome measures

Outcome measures
Measure	Sodium Nitrite n=3 Participants Sodium Nitrite will be administered at three time points: At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs. At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes. Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min. Sodium Nitrite: Same as the details in Arm Description.
Safety of Sodium Nitrite Administration Measured by Methemoglobin Levels	1.45 percentage of methemoglobin Standard Deviation 0.35

PRIMARY outcome

Timeframe: Baseline and 1 hour post infusion

The safety of Sodium Nitrite administration will be assessed by the incidence of fall in patient's Mean Arterial Pressure greater than 20% from recorded baseline requiring discontinuation of drug infusion during and after the nitrite infusion in the transplant recipient. Mean Arterial Pressure will be monitored at 1 minute intervals during study drug infusion followed by 15 minute intervals for 1 hour.

Outcome measures

Outcome measures
Measure	Sodium Nitrite n=3 Participants Sodium Nitrite will be administered at three time points: At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs. At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes. Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min. Sodium Nitrite: Same as the details in Arm Description.
Safety of Sodium Nitrite Administration - Number of Participants With Fall in Patient's Mean Arterial Pressure Greater Than 20%	0 Participants

SECONDARY outcome

Timeframe: First 72 hours post organ reperfusion.

The primary study endpoint is the incidence of grades 2+3 Primary Graft Dysfunction (PGD) based upon the worst PGD grade during the first 72 hours post organ reperfusion. The severity of PGD is graded 0-3 based on the presence or absence of diffuse opacities on chest radiograph and the ratio of arterial oxygen pressure to inspired oxygen concentration. The grading system predicts post-lung transplant outcomes with Grade 3 being the worst.

Outcome measures

Outcome measures
Measure	Sodium Nitrite n=3 Participants Sodium Nitrite will be administered at three time points: At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs. At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes. Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min. Sodium Nitrite: Same as the details in Arm Description.
Number of Participants With Primary Graft Dysfunction Grades 2+3	1 Participants

SECONDARY outcome

Timeframe: Up to 12 months post lung transplant

To evaluate the efficacy of Sodium Nitrite infusion into the procured lungs and the lung transplant recipient in the prevention of delayed allograft complications including the incidence of acute rejection. Prevention of delayed allograft complications include clinically indicated spirometric and lung volume assessments of lung function performed as an indicator of Bronchiolitis Obliterans Syndrome (BOS), and evidence of pathological rejection by surveillance transbronchial lung biopsies.

Outcome measures

Outcome measures
Measure	Sodium Nitrite n=3 Participants Sodium Nitrite will be administered at three time points: At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs. At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes. Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min. Sodium Nitrite: Same as the details in Arm Description.
Number of Participants With Acute Rejection	1 Participants

SECONDARY outcome

Timeframe: Up to 12 months post lung transplant

To evaluate the efficacy of Sodium Nitrite infusion into the procured lungs and the lung transplant recipient in the prevention of delayed allograft complications including the incidence of chronic rejection. Prevention of delayed allograft complications include clinically indicated spirometric and lung volume assessments of lung function performed as an indicator of Bronchiolitis Obliterans Syndrome (BOS), and evidence of pathological rejection by surveillance transbronchial lung biopsies.

Outcome measures

Outcome measures
Measure	Sodium Nitrite n=3 Participants Sodium Nitrite will be administered at three time points: At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs. At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes. Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min. Sodium Nitrite: Same as the details in Arm Description.
Number of Participants With Chronic Rejection	0 Participants

SECONDARY outcome

Timeframe: Baseline through Day 30 post transplantation.

Defined as the number of days off mechanical ventilation at baseline through Day 30 post transplantation.

Outcome measures

Outcome measures
Measure	Sodium Nitrite n=3 Participants Sodium Nitrite will be administered at three time points: At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs. At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes. Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min. Sodium Nitrite: Same as the details in Arm Description.
Number of Ventilator Free Days (VFD)	18 days Standard Deviation 15.6

SECONDARY outcome

Timeframe: Day 30 post transplantation.

Defined as the number of days outside the ICU through Day 30 post transplantation.

Outcome measures

Outcome measures
Measure	Sodium Nitrite n=3 Participants Sodium Nitrite will be administered at three time points: At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs. At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes. Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min. Sodium Nitrite: Same as the details in Arm Description.
Number of ICU Free Days (IFD)	14.7 days Standard Deviation 13.3

Adverse Events

Sodium Nitrite

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sodium Nitrite n=3 participants at risk Sodium Nitrite will be administered at three time points: At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs. At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes. Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min. Sodium Nitrite: Same as the details in Arm Description.
Respiratory, thoracic and mediastinal disorders Respiratory failure	33.3% 1/3 • Number of events 1 • From study enrollment to 72 hours after the last dose of study drug, an average of 1 year

Other adverse events

Other adverse events
Measure	Sodium Nitrite n=3 participants at risk Sodium Nitrite will be administered at three time points: At the time of organ procurement, a pre-prepared syringe of sodium nitrite will be added to each of the 2.8L bags of Perfadex solution to flush the donor lungs. At the time of transplant just prior to reperfusion of lungs, , the donor lungs are flushed with a cold pneumoplegia solution after the bronchial (1st) anastomosis and with warm pneumoplegia solution after the PV (3rd, last) anastomosis. The drug will be added to pneumoplegia solution just prior to both the flushes. Sodium Nitrite will be delivered intravenously to the recipient immediately prior to lung reperfusion as a single infusion at rate of 4 mL/min for the first 30 min, followed by 2.2 mL/min for the next 60 min. Sodium Nitrite: Same as the details in Arm Description.
Respiratory, thoracic and mediastinal disorders Atypical appearance of the lungs	66.7% 2/3 • Number of events 2 • From study enrollment to 72 hours after the last dose of study drug, an average of 1 year

Additional Information

Matthew Morrell, MD

University of Pittsburgh

Phone: 412-647-8477

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place