Safety and Efficacy Study of Nitric Oxide in Patients Going Through Lung Transplantation

NCT ID: NCT00570245

Last Updated: 2016-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-04-30
• Study Completion Date: 2008-06-30

Brief Summary

The purpose of this study is to assess the safety and efficacy of inhaled nitric oxide in prevention of lung graft dysfunction due to ischemia-reperfusion

Detailed Description

• Pilot, single-center, prospective, randomized, parallel-group, controlled, open-label trial.
• Sixty lung donors will be analyzed, making a comparative study between donors receiving NO for 3 hours prior to removal of the organ versus a control group to which NO will not be administered.
• A Swan-Ganz catheter will be placed to determine PVR, PAP, MV, and PCP; and blood gases will be done after arterial cannulation to determine FiO2/PaO2 hourly. Also, standard blood chemistry, hematology, coagulation parameters, and arterial blood gas.
• Prior to NO administration and before procurement, a BAL (bronchoalveolar lavage) will be done to determine the presence of leukocytes, predominantly neutrophils, IL-1, IL-6, IL-8, IL-10, TNF, and proteins as well as obtaining secretions for culture.
• The dosage of NO will be 10ppm, with NO2 and methemoglobinemia being monitored exhaustively.
• In the operating room and prior to lung removal, a new BAL will be done and the anti-inflammatory agents described above will be determined.
• Organ removal and the preservation fluid used will be standard, according to the established surgical protocol.
• Anesthesia: methylprednisolone 1 g will be administered before organ extraction; hemodynamic determinations of mAP, PAP, CVP, MV, and hourly urinary output and arterial blood gas.
• Hemodynamic and respiratory determinations will be made in the lung receptors: mAP, mPAP, PVR, MV, PCP, DO2, Qs/Qt, and CVP as well as gas determinations every 30 minutes, blood chemistry, hematology, and coagulation immediately after reperfusion. A BAL will also be done after anesthesia induction.
• Incidents during surgery will be recorded, especially the need for extracorporeal circulation as well as transfusion requirements and ischemia times.
• After surgery, another BAL will be done both 24 hours and 48 hours after return to the Recovery Unit. Hemodynamic and respiratory parameters will be monitored every 4 hours for the first 48 hours after surgery, as well as arterial blood gases.
• Blood chemistry will be done every 12 hours along with coagulation and hematology tests.
• Chest x-ray on admission and daily to determine the degree of the patient's edema over the first 48 hours.
• Drug administration: the NO will be administered in the respirator intake at a dose of 10ppm for 48 hours. A monitor will be used showing the gas dosage continuously, as well as NO2 and methemoglobinemia.
• The inflammatory agents (TNF, IL-1, IL-2, IL-6, IL-8, and IL-10) will be determined with the ELISA technique.

Conditions

Lung Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Neither donors or recipients will receive NO

Group Type: NO_INTERVENTION

No interventions assigned to this group

B

Donor will not receive NO, recipient will receive up to 48 hours of NO

Group Type: ACTIVE_COMPARATOR

Nitric oxide

Intervention Type: DRUG

inhalation, 10 ppm, for up to 48 hours

C

The donor will receive NO for 3 hours and the recipient will receive NO for up to 48 hours

Group Type: ACTIVE_COMPARATOR

Nitric oxide

Intervention Type: DRUG

inhalation; 10ppm; 3 hours (donor) up to 48 hours (recipient)

Interventions

Nitric oxide

inhalation, 10 ppm, for up to 48 hours

Intervention Type: DRUG

Nitric oxide

inhalation; 10ppm; 3 hours (donor) up to 48 hours (recipient)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Have a lung graft scheduled
• Males and females aged 18 to 65
• Signed informed consent approved by the IRB/EC

Exclusion Criteria

• Uncontrolled bacterial infection
• Creatinine clearance <50 ml/min
• Severe extrapulmonary organic dysfunction
• Continuing smoking habit
• Neoplastic disease (2-5 years free of tumor, depending on type)
• Pregnancy or nursing
• Severe osteoporosis
• Active peptic ulcer
• Progressive neuromuscular disease
• Active limiting systemic disease. Complicated diabetes.
• Any contraindication based on the judgement of the investigator

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mallinckrodt

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rosario Vicente, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital General La Fe

Locations

Hospital General La Fe

Valencia, , Spain

Countries

Spain

References

Moreno I, Vicente R, Ramos F, Vicente JL, Barbera M. Determination of interleukin-6 in lung transplantation: association with primary graft dysfunction. Transplant Proc. 2007 Sep;39(7):2425-6. doi: 10.1016/j.transproceed.2007.07.056.

Reference Type: BACKGROUND

PMID: 17889209 (View on PubMed)

Moreno I, Mir A, Vicente R, Pajares A, Ramos F, Vicente JL, Barbera M. Analysis of interleukin-6 and interleukin-8 in lung transplantation: correlation with nitric oxide administration. Transplant Proc. 2008 Nov;40(9):3082-4. doi: 10.1016/j.transproceed.2008.08.124.

Reference Type: BACKGROUND

PMID: 19010201 (View on PubMed)

Moreno I, Vicente R, Mir A, Leon I, Ramos F, Vicente JL, Barbera M. Effects of inhaled nitric oxide on primary graft dysfunction in lung transplantation. Transplant Proc. 2009 Jul-Aug;41(6):2210-2. doi: 10.1016/j.transproceed.2009.05.019.

Reference Type: BACKGROUND

PMID: 19715875 (View on PubMed)

Other Identifiers

VICER1

Identifier Type: -

Identifier Source: org_study_id