Simvastatin in Colorectal Surgery

Perioperative Care Clinical Trial

— StatCol  

Official title:

Prospective, Double-Blinded, Multi-Centred, Randomised Controlled Trial of Perioperative Simvastatin Use in Elective Colorectal Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00994903
• Other study ID #: StatCol
• Status: Completed
• Phase: Phase 3
• First received: October 13, 2009
• Last updated: November 27, 2013
• Start date: October 2011
• Est. completion date: September 2013

Study information

• Verified date: November 2013
• Source: University of Auckland, New Zealand
• Contact: n/a
• Is FDA regulated: No
• Health authority: New Zealand: Health and Disability Ethics Committees
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 132
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Intestinal Neoplasm
• Intestinal Neoplasms
• Perioperative Care

Intervention

Drug:
• Simvastatin
40mg orally, given 3-7 days pre-op and continued till 14 days post-op
• Placebo
Placebo (Inert calcium lactate) tablets 3-7 days pre-op to 14 days post-op (as per experimental arm)

Locations

Country	Name	City	State
New Zealand	Auckland City Hospital	Auckland
New Zealand	Manukau Surgical Centre, Middlemore Hospital	Auckland
New Zealand	North Shore Hospital	Auckland

Sponsors (4)

Lead Sponsor	Collaborator
University of Auckland, New Zealand	Auckland District Health Board, Counties Manukau Health, Waitemata District Health Board

Country where clinical trial is conducted

New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total complications	Complications pre-defined and graded by the Clavien-Dindo classification	Up to post-operative day 30	No
Secondary	Peritoneal Cytokines		Postoperative Day 1	No
Secondary	Serum cytokines		Post-operative Day 1	No
Secondary	Change in serum C-reactive protein (CRP)		Baseline and Postoperative Day 1, 2 and 3	No
Secondary	Change in functional recovery		Baseline and Postoperative Day 1, 3, 7, 14, and 30	No