Simvastatin in Colorectal Surgery

NCT00994903 | Completed Phase 3

• 1 other identifier: StatCol
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Intestinal Neoplasm; Perioperative Care

Keywords

Statin; Colon; Colorectal; Intestinal Neoplasms; ERAS; Perioperative Care

Outcome Measures

Primary Outcomes (1)

• Total complications

  Complications pre-defined and graded by the Clavien-Dindo classification

  Up to post-operative day 30

Secondary Outcomes (4)

• Peritoneal Cytokines

  Postoperative Day 1

• Serum cytokines

  Post-operative Day 1

• Change in serum C-reactive protein (CRP)

  Baseline and Postoperative Day 1, 2 and 3

• Change in functional recovery

  Baseline and Postoperative Day 1, 3, 7, 14, and 30

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo tablets (Inert calcium lactate)

Drug: Placebo

Simvastatin

EXPERIMENTAL

40mg of Simvastatin given 3-7 days pre-op and continued till 14 days post-op

Drug: Simvastatin

Interventions

Simvastatin DRUG

40mg orally, given 3-7 days pre-op and continued till 14 days post-op

Simvastatin

Placebo DRUG

Placebo (Inert calcium lactate) tablets 3-7 days pre-op to 14 days post-op (as per experimental arm)

Placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Auckland, New Zealand: lead
• Counties Manukau Health: collaborator
• Waitemata District Health Board: collaborator
• Auckland District Health Board: collaborator

Study Sites (3)

Auckland City Hospital

Auckland, New Zealand

Location

Manukau Surgical Centre, Middlemore Hospital

Auckland, New Zealand

Location

North Shore Hospital

Auckland, New Zealand

Location

Related Publications (1)

• Singh PP, Lemanu DP, Soop M, Bissett IP, Harrison J, Hill AG. Perioperative Simvastatin Therapy in Major Colorectal Surgery: A Prospective, Double-Blind Randomized Controlled Trial. J Am Coll Surg. 2016 Aug;223(2):308-320.e1. doi: 10.1016/j.jamcollsurg.2016.04.004. Epub 2016 Apr 13.

  PMID: 27086089 DERIVED

MeSH Terms

Conditions

Intestinal Neoplasms

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Andrew G Hill, MBChB MD FRACS

  University of Auckland, New Zealand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Andrew Hill

Study Record Dates

• First Submitted: October 13, 2009
• First Posted: October 14, 2009
• Study Start: October 1, 2011
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: December 2, 2013

Record last verified: 2013-11

Locations

NZ (3)