Safety and Efficacy Study of Nitric Oxide in Patients Going Through Lung Transplantation - Full Text View

Purpose

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

Condition	Intervention	Phase
Lung Transplantation	Drug: Nitric oxide	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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.

Resource links provided by NLM:

MedlinePlus related topics: Lung Transplantation

Drug Information available for: Nitric oxide

U.S. FDA Resources

Further study details as provided by INO Therapeutics:

Primary Outcome Measures:

Edema and mPAP [ Time Frame: 4 - 48 hours ] [ Designated as safety issue: Yes ]

Enrollment:	49
Study Start Date:	April 2005
Study Completion Date:	June 2008
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
No Intervention: A Neither donors or recipients will receive NO
Active Comparator: B Donor will not receive NO, recipient will receive up to 48 hours of NO	Drug: Nitric oxide inhalation, 10 ppm, for up to 48 hours
Active Comparator: C The donor will receive NO for 3 hours and the recipient will receive NO for up to 48 hours	Drug: Nitric oxide inhalation; 10ppm; 3 hours (donor) up to 48 hours (recipient)

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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00570245

Locations

Spain
Hospital General La Fe
Valencia, Spain, 46009

Sponsors and Collaborators

INO Therapeutics

Investigators

Principal Investigator:

Rosario Vicente, MD

Hospital General La Fe

More Information

Publications:

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.

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.

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.

Responsible Party:	Deborah Petrowsky, INO Therapeutics
ClinicalTrials.gov Identifier:	NCT00570245 History of Changes
Other Study ID Numbers:	VICER1
Study First Received:	December 6, 2007
Last Updated:	January 23, 2013
Health Authority:	European Union: European Medicines Agency

Keywords provided by INO Therapeutics:

Lung transplantation

Additional relevant MeSH terms:

Reperfusion Injury
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications
Pathologic Processes
Nitric Oxide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions

Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Cardiovascular Agents
Protective Agents

ClinicalTrials.gov processed this record on May 23, 2013