Simvastatin in Colorectal Surgery (StatCol)
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Purpose
Statins (HMG-CoA reductase inhibitors) are a widely used class of cholesterol-lowering drugs that have an established role in the medical management of cardiovascular disease. Their benefits have also been shown in the surgical setting with decreased cardiovascular complications and lower perioperative mortality following cardiac and vascular surgery. There is now considerable evidence showing statins have useful pleiotropic properties that extend beyond cholesterol lowering, including anti-inflammatory, anti-oxidant, immunomodulatory and fibrinolytic effects. Growing evidence suggests these effects may be useful in attenuating the proinflammatory and metabolic stress response to surgery and the benefit of statins may extend to other surgical settings such as abdominal surgery.
Laboratory studies demonstrate the surgically-relevant benefits of statins and show they decrease peritoneal inflammation, reduce the severity of intestinal ischaemia-reperfusion injury, improve survival in models of abdominal sepsis, decrease the formation of postoperative intraperitoneal adhesions and improve the healing of colonic anastomoses. Retrospective clinical studies show statins improve outcomes in sepsis, reduce the postoperative systemic inflammatory response syndrome (SIRS) and are associated with decreased rates of surgical wound infections and postoperative respiratory complications following various non-cardiac general surgical procedures. However, no prospective studies have specifically evaluated the perioperative use of statins in abdominal surgery. Using colorectal surgery as a model for major abdominal surgery, the investigators will conduct a randomised controlled trial evaluating the effect of perioperative statin use on postoperative morbidity, local and systemic inflammatory response, and functional recovery after surgery.
| Condition | Intervention | Phase |
|---|---|---|
|
Intestinal Neoplasm Perioperative Care |
Drug: Simvastatin Drug: Placebo |
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: Treatment |
| Official Title: | Prospective, Double-Blinded, Multi-Centred, Randomised Controlled Trial of Perioperative Simvastatin Use in Elective Colorectal Surgery |
- Total complications [ Time Frame: Up to post-operative day 30 ] [ Designated as safety issue: No ]Complications pre-defined and graded by the Clavien-Dindo classification
- Peritoneal Cytokines [ Time Frame: Postoperative Day 1 ] [ Designated as safety issue: No ]
- Serum cytokines [ Time Frame: Post-operative Day 1 ] [ Designated as safety issue: No ]
- Change in serum C-reactive protein (CRP) [ Time Frame: Baseline and Postoperative Day 1, 2 and 3 ] [ Designated as safety issue: No ]
- Change in functional recovery [ Time Frame: Baseline and Postoperative Day 1, 3, 7, 14, and 30 ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 140 |
| Study Start Date: | October 2011 |
| Estimated Study Completion Date: | November 2013 |
| Estimated Primary Completion Date: | November 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Placebo Comparator: Placebo
Placebo tablets (Inert calcium lactate)
|
Drug: Placebo
Placebo (Inert calcium lactate) tablets 3-7 days pre-op to 14 days post-op (as per experimental arm)
|
|
Experimental: Simvastatin
40mg of Simvastatin given 3-7 days pre-op and continued till 14 days post-op
|
Drug: Simvastatin
40mg orally, given 3-7 days pre-op and continued till 14 days post-op
|
Eligibility| Ages Eligible for Study: | 18 Years to 90 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion criteria:
- Consecutive consenting patients undergoing elective colectomy, rectal resection, and reversal of Hartmann's procedure at Middlemore Hospital, Manukau Surgery Centre, Auckland City Hospital, and North Shore Hospital.
Exclusion criteria:
- Acute presentation
- Already taking statins or other lipid-lowering medication
- Known adverse reaction to statins
- Hepatic dysfunction
- Moderate to severe renal dysfunction
- Previous history of rhabdomyolysis
- On contraindicated medication
- Pregnancy
- Breastfeeding
- Patient choice.
Contacts and Locations| Contact: Primal Singh, MBChB | 021 129 3707 | dr.parrysingh@gmail.com |
| New Zealand | |
| Manukau Surgical Centre, Middlemore Hospital | Recruiting |
| Auckland, New Zealand | |
| Contact: Primal Singh, MBChB 021 129 3707 dr.parrysingh@gmail.com | |
| Principal Investigator: Andrew G Hill, MBChB, MD, FRACS | |
| North Shore Hospital | Recruiting |
| Auckland, New Zealand | |
| Contact: Primal Singh, MBChB 021 129 3707 dr.parrysingh@gmail.com | |
| Principal Investigator: Mattias Soop, PhD, FRACS | |
| Auckland City Hospital | Recruiting |
| Auckland, New Zealand | |
| Contact: Primal Singh, MBChB 021 129 3707 dr.parrysingh@gmail.com | |
| Principal Investigator: Ian Bissett, MBChB, MD, FRACS | |
| Principal Investigator: | Andrew G Hill, Assoc Prof | University of Auckland, New Zealand |
More Information
No publications provided
| Responsible Party: | Associate Professor Andrew G. Hill, University of Auckland |
| ClinicalTrials.gov Identifier: | NCT00994903 History of Changes |
| Other Study ID Numbers: | StatCol |
| Study First Received: | October 13, 2009 |
| Last Updated: | January 9, 2012 |
| Health Authority: | New Zealand: Health and Disability Ethics Committees |
Keywords provided by University of Auckland, New Zealand:
|
Statin Colon Colorectal |
Intestinal Neoplasms ERAS Perioperative Care |
Additional relevant MeSH terms:
|
Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases Simvastatin |
Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Lipid Regulating Agents Therapeutic Uses Hydroxymethylglutaryl-CoA Reductase Inhibitors Anticholesteremic Agents Enzyme Inhibitors |
ClinicalTrials.gov processed this record on June 18, 2013