Brief Title
Fast Track Pathway to Accelerated Cholecystectomy
Official Title
Fast Track Pathway to Accelerated Cholecystectomy Versus Standard of Care for Acute cholecysTitis
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.
Study Type
Interventional
Primary Outcome
Feasibility (pertaining to patient recruitment)
Secondary Outcome
Hospital Length of Stay
Condition
Cholecystitis
Intervention
cholecystectomy
Study Arms / Comparison Groups
Standard of Care
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Procedure
Estimated Enrollment
60
Start Date
January 22, 2020
Completion Date
February 2021
Primary Completion Date
December 2020
Eligibility 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Flavia Kessler Borges PhD, M.D, 905-527-4322, [email protected]
Location Countries
Canada
Location Countries
Canada
Administrative Informations
NCT ID
NCT04033822
Organization ID
FAST Pilot
Responsible Party
Sponsor-Investigator
Study Sponsor
P.J. Devereaux
Collaborators
St. Joseph's Health Care London
Study Sponsor
Flavia Kessler Borges PhD, M.D, Principal Investigator, Population Health Research Institute
Verification Date
March 2020