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

Lung Transplantation Clinical Trial

Official title:

A Pilot, Single Center Prospective, With Parallel Groups, Controlled and Open to Evaluate the Efficacy of Nitric Oxide for Inhalation in Lung Donors and in the Prevention of Reperfusion Injury.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00570245
• Other study ID #: VICER1
• Status: Completed
• Phase: Phase 2
• First received: December 6, 2007
• Last updated: October 18, 2016
• Start date: April 2005
• Est. completion date: June 2008

Study information

• Verified date: October 2016
• Source: Mallinckrodt
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines Agency
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Transplantation

Intervention

Drug:
• Nitric oxide
inhalation, 10 ppm, for up to 48 hours
• Nitric oxide
inhalation; 10ppm; 3 hours (donor) up to 48 hours (recipient)

Locations

Country	Name	City	State
Spain	Hospital General La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Mallinckrodt

Country where clinical trial is conducted

Spain, 

References & Publications (3)

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. — View Citation

Moreno I, Vicente R, Mir A, León 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. — View Citation

Moreno I, Vicente R, Ramos F, Vicente JL, Barberá M. Determination of interleukin-6 in lung transplantation: association with primary graft dysfunction. Transplant Proc. 2007 Sep;39(7):2425-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Edema and mPAP		4 - 48 hours	Yes