Bypass Equipoise Sleeve Trial (BEST) (BEST)

Bypass Equipoise Sleeve Trial (BEST); A Randomised Controlled Multicenter Trial Comparing Gastric Bypass and Sleeve Gastrectomy

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Severe Obesity
• Intervention / Treatment: Other: Sleeve gastrectomy; Other: gastric bypass

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.

• Study Type: Interventional
• Enrollment (Actual): 1752
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Tønsberg, Norway
    • Sentralsykehuset Vestfold
• Sweden
  • Falun, Sweden
    • Falu Hospital
  • Gävle, Sweden
    • Gävle hospital
  • Göteborg, Sweden, 416 50
    • Östra Hospital
  • Kalmar, Sweden, 392 85
    • Kalmar County Hospital
  • Lindesberg, Sweden, 701 85
    • Lindesbergs Hospital
  • Linköping, Sweden, S-58183
    • Linköping University
  • Ljungby, Sweden
    • Ljungby Hospital
  • Lycksele, Sweden
    • Lycksele Hospital
  • Mora, Sweden
    • Mora Hospital
  • Norrköping, Sweden
    • Vrinnevi Hospital, Norrköping
  • Skåne, Sweden
    • GB Obesitas
  • Skövde, Sweden, 541 85
    • Skaraborgs Hospital
  • Stockholm, Sweden, 116 91
    • Ersta Hospital
  • Stockholm, Sweden
    • Stockholm South General Hospital
  • Stockholm, Sweden
    • Capio S:t Görans hospital
  • Stockholm, Sweden, 182 88
    • Danderyds Hospital
  • Södertälje, Sweden, 152 86
    • Södertälje Hospital
  • Torsby, Sweden
    • Torsby Hospital
  • Uppsala, Sweden
    • Uppsala University Hospital
  • Örebro, Sweden, 701 85
    • Orebro University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sleeve gastrectomy; Laparoscopic sleeve gastrectomy	Other: Sleeve gastrectomy; Typ of surgery: sleeve gastrectomy
Active Comparator: Gastric bypass; Laparoscopic Roux-en-Y gastric bypass	Other: gastric bypass; Type of surgery: gastric bypass

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight loss	Non-inferiority for SG is defined as < 5% weight difference	5 years
Serious adverse events	Superiority for SG is having 35% less serious (substantial) adverse events compared to RYGB	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality and cause of death	National Cause of Death registry	5, 10, 20 and 30 years
Health care consumption, In hospital registry	Data from In hospital registry (Days in hospital)	5, 10, 20 and 30 years
Health care consumption,	Data from Outpatient registry ( number of visits)	5, 10, 20 and 30 years
Health care consumption	National drug registry (type of drug)	5, 10, 20 and 30 years
Development of co-morbidities from national registry data	National stroke registry, National Cardiac registry, National Diabetes Registry, Cancer registry	5, 10, 20, 30 years
Formal cost effective analysis	Cost per quality-adjusted life-year and life-year)	5, 10 and 20 years
Peri-operative outcome, Complications	Complications; Surgical (minor/major) and medical	Up to 30 days postop
Peri-operative outcome, surgical time	surgical time (min)	Up to 30 days postop
Peri-operative outcome, sick leave	sick leave (days)	Up to 30 days postop
Peri-operative outcome, length of stay	length of stay (days)	Up to 30 days postop
Adverse events	General description of patterns of all adverse events	1, 2, 5 and 10 years
Weight loss	Between baseline and 1 and 2 years	Baseline, 1, 2, 5 and 10 years
Number of patients with arterial cardiovascular events	Composite of myocardial infarction+ stroke+ other occlusive arterial condition	Baseline, 1, 2, 5 and 10 years
Number of patients with venous event	Composite of Deep vein thrombosis+ Pulmonary emboli+ other venous event	Baseline, 1, 2, 5 and 10 years
Number of patients with diabetes requiring drug treatment	Development of diabetes measured as numbers of patients having a diabetes diagnosis and oral medication and injection therapy	Baseline, 1, 2, 5 and 10 years
Number of patients with a psychiatric morbidity	Number of patients with a psychiatric morbidity	Baseline, 1, 2, 5 and 10 years
Number of patients with hypertension treatment	Number of patients with hypertension treatment (any type of Medical treatment)	Baseline, 1, 2, 5 and 10 years
Number of patients diagnosed with a malignancy	Number of patients diagnosed with a malignancy	Baseline, 1, 2, 5 and 10 years
Number of patients with dyslipidemia treatment	Number of patients with diagnosis of dyslipidemia and on oral lipid lowering treatment	Baseline, 1, 2, 5 and 10 years
Weight in men and women	Analyses of the primary outcome weight in men and women	Baseline, 1, 2, 5 and 10 years
serious adverse events in men and women	Analyses of the primary outcome serious adverse events in men and women	Baseline, 1, 2, 5 and 10 years
Weight in patients with BMI >43 vs <43 kg/m2.	Analyses of the primary outcome weight in patients with BMI >43 vs <43 kg/m2.	Baseline, 1, 2, 5 and 10 years
Serious adverse events in patients with BMI >43 vs <43 kg/m2	Analyses of the primary outcome serious adverse events in patients with BMI >43 vs <43 kg/m2.	Baseline, 1, 2, 5 and 10 years
Weight in patients aged 18-25 y, 25-50 y, or >50 y	Analyses of the primary outcome weight in patients aged 18-25 y, 25-50 y, or >50 y	Baseline, 1, 2, 5 and 10 years
Serious adverse events in patients aged 18-25 y, 25-50 y, or >50 y	Analyses of the primary outcome serious adverse events in patients aged 18-25 y, 25-50 y, or >50 y	Baseline, 1, 2, 5 and 10 years
Mineral nutritional status	Serum concentrations of iron depots, zinc, magnesium, selenium and copper	Baseline, 1, 2, 5 and 10 years
Vitamin nutritional status	Serum concentrations of vitamins (Vitamin B12, Vitamin D, Vitamin A, thiamin)	Baseline, 1, 2, 5 and 10 years
Serum concentrations of albumin	Serum concentrations of Albumin	Baseline, 1, 2, 5 and 10 years
Changes in quality of Life assessed with EQ-5D	Assessed with EQ-5D	Baseline, 1, 2, 5 and 10 years
Changes in quality of Life assessed with Obesity Problems (OP)	Assessed with Obesity Problems (OP)	Baseline, 1, 2, 5 and 10 years
Changes in quality of Life assessed with Short Form-36	Assessed with SF-36	Baseline, 1, 2, 5 and 10 years
Alcohol consumption	Assessed by AUDIT	1, 2, 5 and 10 years
Gastro-esophageal reflux disease	Gastro-esophageal reflux disease is defined as present/ not present in at least one of following modalities: Questionnaire DeMeester score, 24h pH manometry and/or gastroscopy	1, 2, 5 and 10 years
Fracture incidence	From clinical data and national registry	2, 5 and 10 years
Bone density and body composition	Dual energy X-ray Absorptiometry (DEXA) in at least a subgroup of 500+500	10 years
Dietary intake	Questionnaire regarding food intake (E14x)	1 and 10 years
Eating patterns	Three Factor Eating Questionnaire (TFEQ)	1 and 10 years
Gastro-intestinal side effects	Questionnaire: Gastro-intestinal Symptom Rating Score (GSRS)	1 and 10 years
Dumping symptoms	Questionnaire: Dumping Symptom Rating Score (DSRS)	1 and 10 years
Adverse events	Clinical data combined with national registry data	30 days postop, 1, 2, 5 and 10 years

Collaborators and Investigators

• Sponsor: Göteborg University
• Collaborators: Danderyd Hospital; Region Örebro County; Uppsala University Hospital; Skaraborg Hospital; Falu Hospital; Stockholm South General Hospital; Sodertalje Hospital; Mora Hospital; Vrinnevi Hospital, Norrköping; Sykehuset i Vestfold HF; Gävle Hospital; Östra Hospital; Kalmar County Hospital; Ersta Hospital, Sweden; Lindesbergs Hospital; Torsby Hospital; Lycksele Hospital; Capio S:t Görans Hospital; Ljungby Hospital; Gjövik Hospital, Norway; GB Obesitas Skane
• Investigators: Principal Investigator: Torsten Olbers, MD, PhD, Linköping University, Dept of BKV

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: November 4, 2015
• First Submitted That Met QC Criteria: May 9, 2016
• First Posted (Estimated): May 10, 2016

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 7, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Obesity, Morbid
• Other Study ID Numbers: 478-15, version 5 2020-03-23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO