Clinical trial NCT02743754: Hyperbaric Oxygen Therapy and Acute Kidney Injury
Official title: Hyperbaric Oxygen Therapy for Cardiac Surgery-Associated Acute Kidney Injury: A First-in-Human Pilot Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Acute Kidney Injury
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2016-04-19
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Kidney injury is a serious complication of cardiac surgery that occurs in up to 30% of patients and increases the risk of adverse outcomes. Kidney injury initiates when oxygen supply to the kidney drops below levels that are needed for normal cellular function, causing tissue oxygen deficiency (hypoxia), activation of the inflammatory cascade, and oxidative stress. Together, these events further impair tissue oxygenation, culminating in impaired kidney function due to cellular injury and death.

There are no effective therapies for kidney injury after cardiac surgery, but there is evidence that recovery is possible if the processes of injury - i.e., impaired oxygen delivery, increased inflammatory response, and oxidative stress - are ameliorated soon after the onset of injury. Hyperbaric oxygen therapy (HBOT) - which entails the intermittent inhalation of 100% oxygen in a hyperbaric chamber at a pressure higher than one absolute atmosphere (\> 760 mmHg) - has been shown to positively affect all of these processes (i.e., to improve tissue oxygenation, reduce inflammation, and reduce oxidative stress). Thus, we hypothesized that HBOT will reduce the severity of kidney injury after cardiac surgery if it is initiated soon after onset of injury. This hypothesis has not been tested in humans, but is supported by animal studies.

In this first-in-human, unblinded, controlled pilot trial, 20 adult patients who develop severe kidney injury soon after cardiac surgery will be randomized (after obtaining informed consent from the patient or surrogate) to standard-of-care or early HBOT. Severe kidney injury will be defined as a ≥30% drop in kidney function within 6 hours of surgery (as determined by change in creatinine from before surgery to Intensive Care Unit (ICU) admission). This degree of injury occurs in \~ 2% of patients and is associated with a 12-fold increase in the risk of complete kidney failure (requiring dialysis) or death. Patients will be excluded if they have any relative or absolute contraindications to HBOT (e.g., severe ventricular dysfunction, ventricular assist device, severe respiratory dysfunction, pneumothorax, bronchospasm).


Eligibility criteria: Inclusion Criteria:

* age \> 18 years
* any cardiac surgery with cardiopulmonary bypass surgery
* ≥30% drop in kidney function within 6 hours of surgery (determined by change in creatinine from before surgery to ICU admission)

Exclusion Criteria:

* Pre-existing renal dysfunction (creatinine \> 177 µmol/L)
* claustrophobia
* seizure disorder
* severe respiratory dysfunction (PaO2/fraction of inspired oxygen (FiO2) ratio \<150 on 100% O2 and Peep of 10)
* active asthma or bronchospasm
* severe chronic obstructive pulmonary disease
* history of spontaneous pneumothorax or untreated pneumothorax
* congestive heart failure with left ventricular ejection fraction \< 30%
* evidence of ongoing myocardial ischemia
* presence of ventricular assist device or intra-aortic balloon pump
* chronic sinusitis
* chronic/ acute otitis media or major ear drum trauma
* current treatment with bleomycin, cisplatin, doxorubicin and disulfiram

Primary outcomes:
measure: Feasibility of the intervention
timeFrame: 7 days
measure: Safety of the intervention as assessed by adverse events
timeFrame: 7 days
Secondary outcomes:
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hopsital University Health Network
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Keyvan Karkouti, MD
role: PRINCIPAL_INVESTIGATOR
References: