Clinical trial NCT01225094: Curcumin to Prevent Complications After Elective Abdominal Aortic Aneurysm (AAA) Repair
Official title: Curcumin to Prevent Perioperative Complications After Elective Abdominal Aortic Aneurysm Repair: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Acute Kidney Injury
Abdominal Aortic Aneurysm
Keywords: AAA
abdominal aortic aneurysm
acute kidney injury
ischemia-reperfusion
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2010-10-20
Enrollment: 606
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this program of research is to determine whether curcumin, a natural health product, can prevent acute kidney injury and other complications after elective AAA repair. If proven safe and effective, curcumin is an inexpensive intervention which can be readily applied to almost 50,000 AAA repairs performed worldwide each year. New knowledge about this intervention may also guide its use in other surgical and medical settings to prevent complications to the kidneys, heart and other organs.

Detailed description: An abdominal aortic aneurysm (AAA) is a ballooning of the abdominal aorta, the major blood vessel of the body. AAA occurs in up to 2% of adults. Surgeons will plan an AAA repair when the aneurysm grows bigger than 5.5cm, because the AAA might burst without repair. Over 47,000 AAA repairs are performed each year. Despite the benefits of AAA repair there are risks, and the kidneys can be severely injured. We will test whether the natural health product curcumin has an effect on biomarkers of inflammation, kidney injury and heart injury from AAA repair. Curcumin appears to fight oxidation and inflammation, which are ways that the body can be injured by surgery. We will study 600 patients who have elective AAA repair. The patients will receive either curcumin or a matching placebo. We will recruit the 600 patients from 10 centres in Ontario. This study will help us determine whether curcumin exerts any biological effect on biomarkers and whether it is well tolerated. If there is evidence of beneficial effects in this 600 patient trial, this will justify a future larger trial to assess the effects of curcumin on outcomes most important to patients, families and their healthcare providers.

Eligibility criteria: Inclusion Criteria:

* Elective repair of an AAA (excludes thoracic or thoracoabdominal aneurysms)
* 18 years of age or older
* Able to provide informed consent
* Has one or more of the following criteria at time of preoperative assessment:
* x Open repair OR
* x Endovascular repair with ≥ 1 of the following criteria:
* o diabetes mellitus treated with insulin or oral hypoglycemic agents
* o age \> 70 years
* o pre-existing renal impairment (baseline serum creatinine level \>177 μmol/L for men or \>146 μmol/L for women)
* If diabetic, is able and willing to collect and record glucose levels at home

Exclusion Criteria:

* emergent or urgent repair (repair \< 3 days from pre-admission visit; ruptured AAA)
* prior renal transplantation
* pregnant or breastfeeding
* active gastrointestinal reflux disease, gastrointestinal ulcers or hepatobiliary disease (including gallstones)
* has active liver disease
* evidence of AKI (\> 50% increase in serum creatinine) in the 30 days prior to repair
* enrolled in another randomized controlled trial
* receipt of ≥ 1 dialysis treatment in the past week
* previous participation in this trial
* repair is scheduled \> 90 days from date of informed consent
* unable to provide written consent
* allergy(ies) to any member of the Zingiberaceae family: turmeric, ginger, curry, cumin, cardamom)
* allergy(ies) to ingredients of the study product or placebo: yellow or red food coloring, gelatin or cellulose
* have a history of major bleeding event in the previous 6 months
* bleeding disorders: a diagnosis of hemophilia, von Willebrand disease, platelets less than 70 for any reason
* history of hypoglycemia in the past 6 months: blood sugar less than or equal to 3.5 mmol/L

Primary outcomes:
measure: Urine IL-18
timeFrame: Post op value
measure: NT-ProBNP
timeFrame: Change in post-operative minus pre-operative plasma NT-Pro BNP
measure: hsCRP
timeFrame: Change in post-operative minus pre-operative plasma hsCRP
measure: Serum creatinine
timeFrame: Change in peak post-operative serum creatinine (umol/L) in the 7 days following AAA repair minus pre-op value
Secondary outcomes:
measure: Binary measures of continuous biomarker outcomes
timeFrame: Continuous
measure: Safety outcomes
timeFrame: Peri-operative period
measure: Composite clinical outcomes adjudicated by investigators unaware of treatment outcomes
timeFrame: Within 30 days of AA repair
Other outcomes:
measure: Other outcome measures
timeFrame: Peri-operative period
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Winnipeg
country: Canada
facility: St. Boniface Hospital
state: Manitoba
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital, Civic Campus
state: Ontario
city: Sudbury
country: Canada
facility: Sudbury Regional Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
Study officials:
affiliation: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
name: Amit X Garg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Garg AX, Devereaux PJ, Hill A, Sood M, Aggarwal B, Dubois L, Hiremath S, Guzman R, Iyer V, James M, McArthur E, Moist L, Ouellet G, Parikh CR, Schumann V, Sharan S, Thiessen-Philbrook H, Tobe S, Wald R, Walsh M, Weir M, Pannu N; Curcumin AAA AKI Investigators. Oral curcumin in elective abdominal aortic aneurysm repair: a multicentre randomized controlled trial. CMAJ. 2018 Oct 29;190(43):E1273-E1280. doi: 10.1503/cmaj.180510.