Clinical trial NCT02767505: Bypass Equipoise Sleeve Trial (BEST)
Official title: Bypass Equipoise Sleeve Trial (BEST); A Randomised Controlled Multicenter Trial Comparing Gastric Bypass and Sleeve Gastrectomy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Severe Obesity
Lead sponsor: Göteborg University
Sponsor class: OTHER
Collaborators: name: Ersta Hospital, Sweden
name: Region Örebro County
name: Kalmar County Hospital
name: Lindesbergs Hospital
name: Danderyd Hospital
name: Skaraborg Hospital
name: Sodertalje Hospital
name: Östra Hospital
name: Mora Hospital
name: Torsby Hospital
name: Stockholm South General Hospital
name: Gävle Hospital
name: Uppsala University Hospital
name: Lycksele Hospital
name: Falu Hospital
name: Vrinnevi Hospital, Norrköping
name: Capio S:t Görans Hospital
name: Ljungby Hospital
name: Sykehuset i Vestfold HF
name: Gjövik Hospital, Norway
name: GB Obesitas Skane
First posted: 2016-05-10
Enrollment: 1752
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1
Primary purpose: TREATMENT

Brief summary: This is nationwide registry-based randomised clinical multicenter trial in which patients will be randomised to gastric bypass (RYGB) or sleeve gastrectomy (SG). The co-primary endpoint are weight control over 5 years and the amount of severe adverse events. Additionally the investigators have predefined a number of secondary endpoints, and the trial has a sufficient number of patients to allow comparisons across subgroups.

Detailed description: Follow-up of the patients will use the routines respectively for regular follow-up on the Scandinavian Obesity Surgery Registry (SOReg) after 6v, 1 year, 2 years, and after 5 years.

In order to evaluate if SG has advantages compared to the previous standard, the investigators want to examine whether SG operations are equivalent (non-inferiority) for weight loss and weight stability five years after surgery in comparison to RYGB, and if SG is associated with fewer long-term complications (superiority). The primary outcome measure emanates from assessment of long term weight management and the frequency of serious complications.

The unforeseen global Covid-19 pandemic resulted in that almost all elective benign surgery in Scandinavia was cancelled from March 2020. Thus, the pandemic had severe consequences on the recruitment to the BEST trial during 2020-2021.

During autumn of 2021 the BEST steering committee decided to perform an additional analysis of the power for primary endpoints.

Additional information (Courcoulas et al, JAMA Surg 2020 March; Howard et al, JAMA Surg 2021 Dec) revealed that the risk of any of the predefined substantial adverse events after bariatric surgery is higher than previously anticipated in the revised power calculation, i.e. \>25% instead of 13%. These figures were confirmed in an analysis of real-world data from the bariatric national quality register SOReg in Sweden which registered all patients undergoing sleeve or bypass in Sweden since 2007.

An independent statistician performed the analysis based on information above, but also on 2-year data in BEST. In conclusion, it was stated:

Two post hoc power analyses were conducted based on the data from February 2022:

1. Weight reduction. In the protocol the following is stated "This sample size will also have \>95% power to evaluate non-inferiority of 5% weight loss difference over 5 years between the two groups, assuming 15 kg standard deviation in weight loss over follow-up with two-sided 2.5% significance level.". The post hoc power calculation is based on the two-year follow up data where an average weight loss for all patients (both groups, N=1031) of 29.3 kg was attained with a Sd=21.6. Given a loss to follow up of 20% from 2 year follow up to the 5-year follow up the sample size is assumed to be (1031\*0.80)/2=413 patients per group. With a non-inferiority level of 5 kg weight loss the power is found to be 90% if n=393 per group, and 95% if n=486 per group (https://www.sealedenvelope.com/power/continuous-noninferior/).
2. Substantial adverse events. This post hoc power calculation is for a superiority test where the rate is assumed to be 25% for the gastric bypass at 5 years and sleeve would have a 35% lower level, i e 25%\*0.65=16.25%. Given a sample of n=413 per group the post hoc power will then be 87.5%.

Taking information above into account and in the interest of not prolonging inclusion period unnecessarily the trial steering committee took a decision to stop inclusion in BEST during spring 2022 (final date 31st of March). At termination of inclusion the number of participants that had been included and operated in BEST were 1752. The trial Data Safety and Monitoring Committee reviewed and supported the decision before termination of recruitment to the BEST trial.

Eligibility criteria: Inclusion Criteria:

* BMI 35-50 kg/m2
* Ability to understand and decide on the merits of the study participation
* Accepted for bariatric surgery
* Must understand the information, and be able to make a decisions about participation in the study

Exclusion Criteria:

* Previous bariatric surgery, anti reflux surgery or other gastric surgery
* Moderate to severe reflux disease, Barretts oesophagus or known hiatus hernia \>4 cm
* Unstable mental illness or other known contraindication to bariatric surgery.
* Planned significant surgery at the same time
* Inflammatory bowel disease
* ongoing drug or substance abuse
* not appropriate to randomise the patient, according to surgeon

Primary outcomes:
measure: Weight loss
timeFrame: 5 years
measure: Serious adverse events
timeFrame: 5 years
Secondary outcomes:
measure: Adverse events
timeFrame: 1, 2, 5 and 10 years
measure: Weight loss
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Number of patients with arterial cardiovascular events
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Number of patients with venous event
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Number of patients with diabetes requiring drug treatment
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Number of patients with a psychiatric morbidity
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Number of patients with hypertension treatment
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Number of patients diagnosed with a malignancy
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Number of patients with dyslipidemia treatment
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Weight in men and women
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: serious adverse events in men and women
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Weight in patients with BMI >43 vs <43 kg/m2.
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Serious adverse events in patients with BMI >43 vs <43 kg/m2
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Weight in patients aged 18-25 y, 25-50 y, or >50 y
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Serious adverse events in patients aged 18-25 y, 25-50 y, or >50 y
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Mineral nutritional status
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Vitamin nutritional status
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Serum concentrations of albumin
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Changes in quality of Life assessed with EQ-5D
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Changes in quality of Life assessed with Obesity Problems (OP)
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Changes in quality of Life assessed with Short Form-36
timeFrame: Baseline, 1, 2, 5 and 10 years
measure: Alcohol consumption
timeFrame: 1, 2, 5 and 10 years
measure: Gastro-esophageal reflux disease
timeFrame: 1, 2, 5 and 10 years
measure: Fracture incidence
timeFrame: 2, 5 and 10 years
measure: Bone density and body composition
timeFrame: 10 years
measure: Mortality and cause of death
timeFrame: 5, 10, 20 and 30 years
measure: Health care consumption, In hospital registry
timeFrame: 5, 10, 20 and 30 years
measure: Health care consumption,
timeFrame: 5, 10, 20 and 30 years
measure: Health care consumption
timeFrame: 5, 10, 20 and 30 years
measure: Development of co-morbidities from national registry data
timeFrame: 5, 10, 20, 30 years
measure: Formal cost effective analysis
timeFrame: 5, 10 and 20 years
measure: Dietary intake
timeFrame: 1 and 10 years
measure: Eating patterns
timeFrame: 1 and 10 years
measure: Gastro-intestinal side effects
timeFrame: 1 and 10 years
measure: Dumping symptoms
timeFrame: 1 and 10 years
measure: Adverse events
timeFrame: 30 days postop, 1, 2, 5 and 10 years
measure: Peri-operative outcome, Complications
timeFrame: Up to 30 days postop
measure: Peri-operative outcome, surgical time
timeFrame: Up to 30 days postop
measure: Peri-operative outcome, sick leave
timeFrame: Up to 30 days postop
measure: Peri-operative outcome, length of stay
timeFrame: Up to 30 days postop
Other outcomes:
Locations:
city: Tønsberg
country: Norway
facility: Sentralsykehuset Vestfold
city: Falun
country: Sweden
facility: Falu Hospital
city: Gävle
country: Sweden
facility: Gävle Hospital
city: Göteborg
country: Sweden
facility: Östra Hospital
city: Kalmar
country: Sweden
facility: Kalmar County Hospital
city: Lindesberg
country: Sweden
facility: Lindesbergs Hospital
city: Linköping
country: Sweden
facility: Linköping University
city: Ljungby
country: Sweden
facility: Ljungby Hospital
city: Lycksele
country: Sweden
facility: Lycksele Hospital
city: Mora
country: Sweden
facility: Mora Hospital
city: Norrköping
country: Sweden
facility: Vrinnevi Hospital, Norrköping
city: Skåne
country: Sweden
facility: GB Obesitas
city: Skövde
country: Sweden
facility: Skaraborgs Hospital
city: Stockholm
country: Sweden
facility: Ersta Hospital
city: Stockholm
country: Sweden
facility: Danderyds Hospital
city: Stockholm
country: Sweden
facility: Capio S:t Görans Hospital
city: Stockholm
country: Sweden
facility: Stockholm South General Hospital
city: Södertälje
country: Sweden
facility: Södertälje Hospital
city: Torsby
country: Sweden
facility: Torsby Hospital
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
city: Örebro
country: Sweden
facility: Örebro University Hospital
Study officials:
affiliation: Linköping University, Dept of BKV
name: Torsten Olbers, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hedberg S, Olbers T, Peltonen M, Osterberg J, Wiren M, Ottosson J, Thorell A; BEST study group. BEST: Bypass equipoise sleeve trial; rationale and design of a randomized, registry-based, multicenter trial comparing Roux-en-Y gastric bypass with sleeve gastrectomy. Contemp Clin Trials. 2019 Sep;84:105809. doi: 10.1016/j.cct.2019.07.001. Epub 2019 Jul 4.