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

Mallinckrodt

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Conditions

Kidney Transplantation

Interventions

Inhaled carbon monoxideDRUG

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

Inhaled carbon monoxideDRUG

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

Inhaled carbon monoxideDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (3)

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

Outcomes

Primary Outcomes

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 Outcomes

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

Data from ClinicalTrials.gov

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