Curcumin to Prevent Complications After Elective Abdominal Aortic Aneurysm (AAA) Repair - Full Text View

Purpose

The purpose of this study 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	Intervention	Phase
Acute Kidney Injury Abdominal Aortic Aneurysm	Drug: curcumin Other: placebo	Phase 2 Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	Curcumin to Prevent Perioperative Complications After Elective Abdominal Aortic Aneurysm Repair: a Randomized Controlled Trial

Resource links provided by NLM:

MedlinePlus related topics: Aneurysms Aortic Aneurysm

Drug Information available for: Curcumin

Genetic and Rare Diseases Information Center resources: Abdominal Aortic Aneurysm

U.S. FDA Resources

Further study details as provided by Lawson Health Research Institute:

Primary Outcome Measures:

serum creatinine [ Time Frame: change from baseline to post-op day 4 to 90 day followup ] [ Designated as safety issue: No ]
We will examine the between group difference in change in peak serum creatinine after repair. Serum creatinine is an established marker for the measurement of kidney function, and has been used in hundreds of randomized trials.

Secondary Outcome Measures:

Acute Kidney Injury [ Time Frame: From baseline creatinine values to post operative day 3 ] [ Designated as safety issue: No ]
AKI is defined by serum creatinine elevations or use of dialysis.
Clinical Events [ Time Frame: From time of randomization to 90 day followup ] [ Designated as safety issue: Yes ]
Overall event rates: Death, bleeding, cardiac events, pneumonia, sepsis/infection, new acute peptic ulcers, stroke, deep vein thrombosis/pulmonary embolism, congestive heart failure, lower limb amputation, pain (as of post-op day 2), nausea or diarrhea, hospital length of stay
Clinical events [ Time Frame: Randomization to 90 day follow-up ] [ Designated as safety issue: Yes ]
Assessment of GI side effects: considering proportion of participants with episode of vomiting and diarrhea during the time they took the investigational medication.
Clinical event [ Time Frame: Randomization to 90 day followup ] [ Designated as safety issue: Yes ]
Serum troponin: established marker for MI and infarction. We will measure values on the post-repair day 1 and compare proportion of each group who have detectable increase.


Estimated Enrollment:	3500
Study Start Date:	November 2011
Estimated Study Completion Date:	July 2015
Estimated Primary Completion Date:	March 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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. 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. 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 (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. Final dose (2000 mg) is administered the morning after repair.	Other: placebo The placebo will look, smell, taste, and in every way be identical to the active drug. 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. Other Name: No brand name applicable.

Arms

Assigned Interventions

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. 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. 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 (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. Final dose (2000 mg) is administered the morning after repair.

Other: placebo

The placebo will look, smell, taste, and in every way be identical to the active drug. 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.

Other Name: No brand name applicable.

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 can prevent the development of kidney injury and other problems from AAA repair. Curcumin appears to fight oxidation and inflammation, which are ways that the body can be injured by surgery. We will perform the first phase (Phase A) of this trial by studying 600 patients who have AAA repair. The patients will receive either curcumin or a placebo. We will recruit patients from 10 centres in Ontario. Phase A will help us assess side effects and see if curcumin can help prevent kidney injury. If curcumin is beneficial and well-tolerated we will expand the study to the next phase. The next phase (Phase B) will have a total of 3600 patients and will look at outcomes most important to patients and their physicians.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01225094

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
St. Michael's Hospital
Toronto, Ontario, Canada, M5B1W8
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N3M5
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

No publications provided


Responsible Party:	Amit Garg, Professor, Medicine, Epidemiology & Biostatistics, Lawson Health Research Institute
ClinicalTrials.gov Identifier:	NCT01225094 History of Changes
Other Study ID Numbers:	16593
Study First Received:	October 19, 2010
Last Updated:	February 12, 2015
Health Authority:	Canada: Health Canada

Keywords provided by Lawson Health Research Institute:


AAA abdominal aortic aneurysm acute kidney injury ischemia-reperfusion

Additional relevant MeSH terms:


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

ClinicalTrials.gov processed this record on February 27, 2015