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

• ClinicalTrials.gov Identifier: NCT00531856
• Recruitment Status: Withdrawn
• First Posted: September 19, 2007
• Last Update Posted: October 19, 2016
• Sponsor: Mallinckrodt
• Information provided by (Responsible Party): Mallinckrodt

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Kidney Transplantation	Drug: Inhaled carbon monoxide; Drug: Inhaled Carbon Monoxide	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: A Prospective, Multicenter, Single-blind, Placebo-controlled, Safety and Tolerability Study of the Effects of Carbon Monoxide for Inhalation in Patients Receiving Kidney Transplants.
• Study Start Date: August 2007
• Actual Primary Completion Date: August 2011
• Actual Study Completion Date: August 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; 5.97 mg/L of carbon monoxide in 30% oxygen	Drug: Inhaled carbon monoxide; 0.7 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant; Drug: Inhaled carbon monoxide; 2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant; Drug: Inhaled carbon monoxide; 3.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant; Drug: Inhaled Carbon Monoxide; 3.5 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant; Drug: Inhaled Carbon Monoxide; 2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant.
Placebo Comparator: 2; Oxygen 30% in Nitrogen	Drug: Inhaled carbon monoxide; 0.7 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant; Drug: Inhaled carbon monoxide; 2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours post transplant; Drug: Inhaled carbon monoxide; 3.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant; Drug: Inhaled Carbon Monoxide; 3.5 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant; Drug: Inhaled Carbon Monoxide; 2.0 mg/kg carbon monoxide/placebo over one hour administered 12-48 hours during transplant.

Outcome Measures

Primary Outcome Measures :

1. Evaluate the safety and tolerability of three carbon monoxide dose levels when administered as an inhaled gas for 1 hour in patients receiving kidney transplants [ Time Frame: 28 days ]

Secondary Outcome Measures :

1. Characterize the pharmacokinetics of the inhaled carbon monoxide; Correlate the safety parameters to inhaled carbon monoxide and COHb levels; Assess laboratory values; Assess potential markers for the incidence of delayed graft function [ Time Frame: 28 days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, California

Universtiy of CA, San Francisco

San Francisco, California, United States, 94143

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

United States, Massachusetts

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

Sponsors and Collaborators

Mallinckrodt

More Information

• Responsible Party: Mallinckrodt
• ClinicalTrials.gov Identifier: NCT00531856
• Other Study ID Numbers: C201
• First Posted: September 19, 2007
• Last Update Posted: October 19, 2016
• Last Verified: October 2016

Keywords provided by Mallinckrodt:

Kidney Transplant, Carbon Monoxide

Additional relevant MeSH terms:

Carbon Monoxide; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Gasotransmitters; Neurotransmitter Agents; Physiological Effects of Drugs