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

Acute Kidney Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01225094
• Other study ID #: 16593
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: October 19, 2010
• Last updated: March 6, 2017
• Start date: November 2011
• Est. completion date: August 2016

Study information

• Verified date: March 2017
• Source: Lawson Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 606
• Est. completion date: August 2016
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Abdominal Aortic Aneurysm
• Acute Kidney Injury
• Aneurysm
• Aortic Aneurysm
• Aortic Aneurysm, Abdominal

Intervention

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:
• 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.

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Maisonneuve-Rosemont Hospital	Montreal	Quebec
Canada	The Ottawa Hospital, Civic Campus	Ottawa	Ontario
Canada	Sudbury Regional Hospital	Sudbury	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	St. Boniface Hospital	Winnipeg	Manitoba

Sponsors (2)

Lead Sponsor	Collaborator
Lawson Health Research Institute	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Other outcome measures	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	Peri-operative period
Primary	Urine IL-18	We will examine the evidence of curcumin on biomarkers and whether it is well tolerated	Post op value
Primary	NT-ProBNP		Change in post-operative minus pre-operative plasma NT-Pro BNP
Primary	hsCRP		Change in post-operative minus pre-operative plasma hsCRP
Primary	Serum creatinine		Change in peak post-operative serum creatinine (umol/L) in the 7 days following AAA repair minus pre-op value
Secondary	Binary measures of continuous biomarker outcomes	e.g acute kidney injury defined using accepted criteria	Continuous
Secondary	Safety outcomes	Anemia, hypoglycemia, diarrhea, bleeding, peptic ulcer, nausea	Peri-operative period
Secondary	Composite clinical outcomes adjudicated by investigators unaware of treatment outcomes	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	Within 30 days of AA repair

External Links

•   Drug Information available for: Curcumin
•   Genetic and Rare Diseases Information Center resources: Abdominal Aortic Aneurysm
•   Medline Plus related topics: Aneurysms Aortic Aneurysm
•   U.S. FDA Resources