Safety and Tolerability Study of Inhaled Carbon Monoxide in Kidney Transplant Patients

NCT ID: NCT00531856

Last Updated: 2016-10-19

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2011-08-31

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of two carbon monoxide doses when administered as an inhaled gas for 1 hour in patients receiving kidney transplants.

Detailed Description

The mechanisms by which carbon monoxide exerts its effects in preventing damage of the graft appear to vary among the models and organs with the common theme of carbon monoxide acting as a potent anti-inflammatory molecule. Carbon monoxide affects several intracellular signaling pathways. In addition, carbon monoxide generates increased levels of anti-inflammatory molecules.

Evaluate the safety and tolerability of three carbon monoxide dose levels consisting of a single 0.7 mg/kg dose and a single 2.0 mg/kg dose when administered post-operatively and a single 2.0 mg/kg dose, a single 3.0mg/kg dose and a 3.5 mg/kg dose when administered intra-operatively as an inhaled gas for 1 hour, by assessment of adverse events (AEs), vital signs, laboratory variables, serum carboxyhemoglobin (COHb), oxygenation, electrocardiography (ECG), and neurocognitive status in patients receiving kidney transplants.

Conditions

Kidney Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

1

5.97 mg/L of carbon monoxide in 30% oxygen

Group Type: EXPERIMENTAL

Inhaled carbon monoxide

Intervention Type: DRUG

0.7 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant

Inhaled carbon monoxide

Intervention Type: DRUG

2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant

Inhaled carbon monoxide

Intervention Type: DRUG

3.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant

Inhaled Carbon Monoxide

Intervention Type: DRUG

3.5 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant

Inhaled Carbon Monoxide

Intervention Type: DRUG

2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant.

2

Oxygen 30% in Nitrogen

Group Type: PLACEBO_COMPARATOR

Inhaled carbon monoxide

Intervention Type: DRUG

0.7 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant

Inhaled carbon monoxide

Intervention Type: DRUG

2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant

Inhaled carbon monoxide

Intervention Type: DRUG

3.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant

Inhaled Carbon Monoxide

Intervention Type: DRUG

3.5 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant

Inhaled Carbon Monoxide

Intervention Type: DRUG

2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant.

Interventions

Inhaled carbon monoxide

0.7 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant

Intervention Type: DRUG

Inhaled carbon monoxide

2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant

Intervention Type: DRUG

Inhaled carbon monoxide

3.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant

Intervention Type: DRUG

Inhaled Carbon Monoxide

3.5 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant

Intervention Type: DRUG

Inhaled Carbon Monoxide

2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female receiving a kidney transplant from any donor type
• BMI between 16 and 36 inclusive
• Spontaneously breathing (non-intubated) with supplemental oxygen standardized at 2 liters via nasal cannula
• Hemodynamically stable with a systolic arterial pressure > 90 mmHg and a heart rate < 120 beats/min
• Acceptable transplantation candidate as judged by medical history, physical exam, ECG, vital signs, clinical chemistry, hematology, and urinalysis
• Given written and verbal information and had the opportunity to ask questions about the study
• Signed informed consent to participate in the study

Exclusion Criteria

• Exposure to any carbon monoxide source (e.g., fire, gas, or heavily polluted air) during the 48 hours prior to the study day
• Baseline blood level of COHb >2%
• Baseline hemoglobin (Hb) <10.0 g/dL
• Patients with significant underlying lung disease such as moderate or severe asthma, COPD, and interstitial lung disease
• Baseline oxygen saturation <95%
• Pregnancy or breastfeeding
• Participation in other clinical trial within 2 months prior to study drug treatment

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

Sponsors

Mallinckrodt

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Universtiy of CA, San Francisco

San Francisco, California, United States

Northwestern University

Chicago, Illinois, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

C201

Identifier Type: -

Identifier Source: org_study_id