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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

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Study Type :	Interventional (Clinical Trial)
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 :	November 2011
Actual Primary Completion Date :	November 2014
Actual Study Completion Date :	August 2016

Arms and Interventions

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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 Name: 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 Name: No brand name applicable.

Outcome Measures

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Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Binary measures of continuous biomarker outcomes [ Time Frame: Continuous ]
   e.g acute kidney injury defined using accepted criteria
2. Safety outcomes [ Time Frame: Peri-operative period ]
   Anemia, hypoglycemia, diarrhea, bleeding, peptic ulcer, nausea
3. Composite clinical outcomes adjudicated by investigators unaware of treatment outcomes [ Time Frame: 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:

1. Other outcome measures [ Time Frame: 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

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Locations

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

Sponsors and Collaborators

Lawson Health Research Institute

Canadian Institutes of Health Research (CIHR)

Investigators

Principal Investigator:	Amit X Garg, MD, PhD	Lawson Health Research Institute

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Medline Plus related topics: Aneurysms Aortic Aneurysm 

Drug Information available for: Curcumin 

Genetic and Rare Diseases Information Center resources: Abdominal Aortic Aneurysm 

U.S. FDA Resources 

Responsible Party:	Amit Garg, Professor, Medicine, Epidemiology & Biostatistics, Lawson Health Research Institute
ClinicalTrials.gov Identifier:	NCT01225094 History of Changes
Other Study ID Numbers:	16593
First Posted:	October 20, 2010
Last Update Posted:	March 7, 2017
Last Verified:	March 2017

Keywords provided by Amit Garg, Lawson Health Research Institute:

AAA; abdominal aortic aneurysm; acute kidney injury; ischemia-reperfusion

Additional relevant MeSH terms:

Aneurysm; Acute Kidney Injury; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Vascular Diseases; Cardiovascular Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Aortic Diseases; Curcumin	Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action