Clinical trial NCT00531856: Safety and Tolerability Study of Inhaled Carbon Monoxide in Kidney Transplant Patients
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 type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Kidney Transplantation
Keywords: Kidney Transplant, Carbon Monoxide
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
First posted: 2007-09-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: 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
timeFrame: 28 days
Secondary outcomes:
measure: 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
timeFrame: 28 days
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Universtiy of CA, San Francisco
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
References: