Curcumin to Prevent Complications After Elective Abdominal Aortic Aneurysm (AAA) Repair

Sponsor

Lawson Health Research Institute (Other)

Overall Status

Completed

CT.gov ID

NCT01225094

Collaborator

Canadian Institutes of Health Research (CIHR) (Other)

606

Enrollment

Locations

Arms

Duration (Months)

60.6

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury Abdominal Aortic Aneurysm	Drug: curcumin Other: placebo	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

606 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Curcumin to Prevent Perioperative Complications After Elective Abdominal Aortic Aneurysm Repair: a Randomized Controlled Trial

Study Start Date :

Nov 1, 2011

Actual Primary Completion Date :

Nov 1, 2014

Actual Study Completion Date :

Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: curcumin Patients will take the study medication (500 mg x 4 capsules, twice daily [BID]) for two days leading up to repair, totaling 4000 mg per day. They will take a dose (2000 mg) the morning of repair, at the same time as regular medications not held for surgery. While they are on call to the operating room, they will take another dose of 2000 mg., and then another 2000 mg dose 6 hours after the repair. Final dose (2000 mg)is administered morning after repair.	Drug: curcumin Patients will take the study medication (500 mg x 4 capsules, twice daily [BID]) for two days leading up to repair, totaling 4000 mg per day. They will take a dose (2000 mg) the morning of repair, at the same time as regular medications not held for surgery. While they are on call to the operating room, they will take another dose of 2000 mg and then another 2000 mg dose 6 hours after the repair. Final dose is administered the morning after repair. Other Names: NHPID name: curcumin
Placebo Comparator: placebo The placebo will look, smell, taste, and in every way be identical to the active drug. Patients will take the study medication in the exact same manner as the curcumin regimen.	Other: placebo The placebo will look, smell, taste, and in every way be identical to the active drug. Patients will take the study medication in the exact same manner as the curcumin regimen. Other Names: No brand name applicable.

Arm

Intervention/Treatment

Experimental: curcumin

Patients will take the study medication (500 mg x 4 capsules, twice daily [BID]) for two days leading up to repair, totaling 4000 mg per day. They will take a dose (2000 mg) the morning of repair, at the same time as regular medications not held for surgery. While they are on call to the operating room, they will take another dose of 2000 mg., and then another 2000 mg dose 6 hours after the repair. Final dose (2000 mg)is administered morning after repair.

Drug: curcumin

Patients will take the study medication (500 mg x 4 capsules, twice daily [BID]) for two days leading up to repair, totaling 4000 mg per day. They will take a dose (2000 mg) the morning of repair, at the same time as regular medications not held for surgery. While they are on call to the operating room, they will take another dose of 2000 mg and then another 2000 mg dose 6 hours after the repair. Final dose is administered the morning after repair.

Other Names:

NHPID name: curcumin

Placebo Comparator: placebo

The placebo will look, smell, taste, and in every way be identical to the active drug. Patients will take the study medication in the exact same manner as the curcumin regimen.

Other: placebo

The placebo will look, smell, taste, and in every way be identical to the active drug. Patients will take the study medication in the exact same manner as the curcumin regimen.

Other Names:

No brand name applicable.

Outcome Measures

Primary Outcome Measures

Urine IL-18 [Post op value]
We will examine the evidence of curcumin on biomarkers and whether it is well tolerated
NT-ProBNP [Change in post-operative minus pre-operative plasma NT-Pro BNP]
hsCRP [Change in post-operative minus pre-operative plasma hsCRP]
Serum creatinine [Change in peak post-operative serum creatinine (umol/L) in the 7 days following AAA repair minus pre-op value]

Secondary Outcome Measures

Binary measures of continuous biomarker outcomes [Continuous]
e.g acute kidney injury defined using accepted criteria
Safety outcomes [Peri-operative period]
Anemia, hypoglycemia, diarrhea, bleeding, peptic ulcer, nausea
Composite clinical outcomes adjudicated by investigators unaware of treatment outcomes [Within 30 days of AA repair]
New acute dialysis, myocardial infarction, receipt of coronary revascularization, sepsis, pneumonia, non-fatal cardiac arrest, stroke, deep vein thrombosis, pulmonary embolism, lower limb amputation, ischemic bowel, congestive heart failure, death

Other Outcome Measures

Other outcome measures [Peri-operative period]
Study medication adherence, length of hospital stay, pain, blood pressure 3 hours after repair, urine output 3 hours after repair, other urine and blood biomarkers, tracer outcomes

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Calgary	Calgary	Alberta	Canada	T3B 6A8
2	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
3	St. Boniface Hospital	Winnipeg	Manitoba	Canada	R2H 2A6
4	Hamilton General Hospital	Hamilton	Ontario	Canada	L8L 2X2
5	London Health Sciences Centre	London	Ontario	Canada	N6G 5W9
6	The Ottawa Hospital, Civic Campus	Ottawa	Ontario	Canada	K1Y4E9
7	Sudbury Regional Hospital	Sudbury	Ontario	Canada	P3E5J1
8	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N3M5
9	St. Michael's Hospital	Toronto	Ontario	Canada	M5B1W8
10	Maisonneuve-Rosemont Hospital	Montreal	Quebec	Canada	H1T 2M4