Fast Track Pathway to Accelerated Cholecystectomy

NCT ID: NCT04033822

Last Updated: 2025-05-01

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-22
• Study Completion Date: 2025-05-15

Brief Summary

More than 10% of Canadians have gallstones, and approximately 10% of these individuals will develop gallbladder inflammation related to gallstones, which is referred to as acute cholecystitis (AC). Patients with AC who do not have their gallbladder surgically removed have a 30% risk of serious complications that can lead to death. Surgery is the only definitive treatment for AC, however, there is controversy regarding the ideal timing of surgery. The two main approaches are early surgery (typically within 7 days of diagnosis) or delayed surgery (7 days to 6 weeks after diagnosis). Although preliminary evidence suggests that early surgery is associated with shorter hospital length of stay, lower risk for complications, and lower costs, practice varies widely regarding the timing of surgery. The limitations of the existing studies include small sample sizes, varied definitions of early versus delayed surgery, and an imbalance of risk between study groups. The proposed pilot study aims to inform the design of a large clinical trial that will compare the outcomes of patients with AC who receive accelerated surgery (i.e., as soon as possible with a goal of surgery within 6 hours of diagnosis) with those who receive standard care.

Detailed Description

The prevalence of gallstones is 10% and approximately 10% of patients develop acute cholecystitis (AC). AC prevalence increases with age and complications are as high as 30% in patients who do not undergo surgery, the only definitive treatment. There is controversy regarding ideal surgical timing. Previously, delayed surgery was thought to decrease bile duct injuries resulting from active inflammation. However, the state of persistent inflammation, hypercoagulability, and stress can cause medical complications such as myocardial injury. Chronic inflammation can lead to fibrosis, adhesions and higher chance of bile duct injuries during delayed surgery. There is also concern for recurrent AC episodes, recurrent pain, biliary pancreatitis, cholangitis or sepsis.

Recent studies suggest that early surgery may be associated with better outcomes, but practice remains variable, ranging anywhere from early surgery (<7 days) to delayed surgery (>7 days). Among >24,000 Ontarians with AC admitted to 106 hospitals, timing of cholecystectomy varied widely across sites. Only 58% of patients underwent surgery within 7 days. High volume hospitals were more likely to perform early surgery.17

Among 14,200 Ontarians with AC, a propensity score analysis demonstrated that early surgery was associated with less bile duct injury (relative risk (RR)=0.53, 95% confidence interval (CI) 0.31-0.90) and shorter length of hospital stay (LOS) (mean 1.9 days, 95% CI 1.7-2.1). Early surgery was less costly and more effective than delayed cholecystectomy.

Trials of surgical timing in patients with AC are limited. The largest randomized controlled trial (RCT) compared early and delayed surgery for AC only included 618 patients.9 Cholecystectomy was performed a median of 1 day after randomization in the early group compared to a median of 25 days in the delayed group. Duration of surgery and conversion rate to open surgery were similar in both groups. Early surgery was associated with less morbidity (11.8% vs. 34.4%, p<0.001), shorter LOS (5.4 vs. 10.0 days, p<0.001), and lower cost (€2919 vs. €4262, p<0.001).

Multiple meta-analyses have suggested that early surgery for AC is associated with fewer wound infections (RR 0.57; 95% CI 0.35-0.93) and have suggested a trend to fewer complications (RR 0.66; 95% CI 0.42-1.03). Limitations of these meta-analyses include studies with small sample sizes, few events, wide confidence intervals, and variation in the definition of early surgery. Finally, there is a lack of strong evidence to make definitive conclusions regarding impact of early surgery in AC, which has led to substantial variation in clinical practice.

AC initiates inflammatory, hypercoagulable, and stress states that can cause medical complications. Early surgical treatment will reduce the time patients are exposed to these harmful states and therefore may reduce the risk of complications. Furthermore, rapid surgery results in a shorter period of AC, which may impact hospital costs. The goal is to undertake a large multicentre RCT of the impact of accelerated surgery (goal within 6 hours of diagnosis) vs. usual timing of surgery in patients with AC on a composite outcome of major clinical and surgical complications at 90 days. "Standard of care", as described, is highly variable and depends on the surgeon and hospital practice patterns.

The main objective of this pilot study is to assess the feasibility of a large trial. The team hypothesizes that accelerated surgery for AC will improve clinical and surgical outcomes. A large RCT on this topic is needed for the following reasons: 1) time to surgery is a modifiable factor; 2) available data are encouraging, but not definitive; 3) there is variation in clinical practice across Ontario and internationally 4) the definition of early surgery has varied substantially across studies; 5) available data may be substantially underestimating the effect of timing of surgery because no trial has evaluated surgery within 6 hours of diagnosis; 6) high-quality evidence will modify clinical practice; and 7) implementation of accelerated surgery could save millions of healthcare dollars annually.

Conditions

Cholecystitis; Cholecystectomy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Standard of Care

Patients randomized to the standard of care arm of the trial will not receive accelerated cholecystectomy surgery to correct cholecystitis. No services will be taken away but patients will continue with care as originally provided by the healthcare system.

Group Type: NO_INTERVENTION

No interventions assigned to this group

FAST Intervention

Patients diagnosed with cholecystitis and randomized to the FAST intervention arm of the study will undergo surgery as soon as possible with a goal of surgery within 6 hours of diagnosis.

Group Type: EXPERIMENTAL

cholecystectomy

Intervention Type: PROCEDURE

If patients are randomized to the intervention arm of the study; said patient will undergo corrective cholecystectomy surgery to correct cholecystitis as soon as possible with a goal of surgery within 6 hours of diagnosis.

Interventions

cholecystectomy

If patients are randomized to the intervention arm of the study; said patient will undergo corrective cholecystectomy surgery to correct cholecystitis as soon as possible with a goal of surgery within 6 hours of diagnosis.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. Age ≥45 years; or age ≥18 years and <45 years with at least one of the following co-morbidities: diabetes or chronic respiratory, cardiovascular, or renal disease;

2. Diagnosis of acute cholecystitis defined by the presence of at least 2 of the following:

1. Abdominal pain in upper right quadrant,

2. Murphy's sign,

3. Leukocytosis >10 × 103/μl, or

4. Oral temperature <36.5°C or >38°C;

3. Cholelithiasis (stones/sludge);

4. Ultrasound signs of cholecystitis;

5. Acute cholecystitis that requires surgery and is diagnosed during working hours;

6. Expected to require at least an overnight hospital admission after surgery; and

7. Provide written informed consent to participate in FAST.

Exclusion Criteria

1. Patients requiring emergent surgery or emergent interventions for another reason;

2. Patients whose therapeutic anticoagulation is not reversible;

3. Patients with a history of heparin-induced thrombocytopenia and current use of warfarin with an INR ≥1.5;

4. Pregnant patients;

5. Previous participation in the trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Joseph's Health Care London

OTHER

Sponsor Role: collaborator

P.J. Devereaux

OTHER

Sponsor Role: lead

Responsible Party

P.J. Devereaux

PHRI Perioperative and Digital Health Research Director

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Flavia Kessler Borges PhD, M.D

Role: PRINCIPAL_INVESTIGATOR

Population Health Research Institute

Rahima Nenshi Msc, M.D

Role: PRINCIPAL_INVESTIGATOR

St. Joseph's Health Care London

PJ Devereaux PhD, M.D

Role: PRINCIPAL_INVESTIGATOR

Hamilton Health Sciences Corporation

Locations

Hamilton General Hospital

Hamilton, Ontario, Canada

Juravinski Hospital

Hamilton, Ontario, Canada

St. Joseph's Healthcare

Hamilton, Ontario, Canada

Lawson Health Research Institute, London Health Sciences Centre

London, Ontario, Canada

Countries

Canada

References

Borges FK, Nenshi R, Serrano PE, Engels P, Vogt K, Park LJ, Di Sante E, Vincent J, Tsiplova K, Devereaux PJ. Fast Track Pathway to Accelerated Cholecystectomy Versus Standard of Care for Acute Cholecystitis (FAST) pilot trial. Can J Surg. 2025 Apr 11;68(2):E122-E131. doi: 10.1503/cjs.016423. Print 2025 Mar-Apr.

Reference Type: DERIVED

PMID: 40216437 (View on PubMed)

Other Identifiers

FAST Pilot

Identifier Type: -

Identifier Source: org_study_id