Clinical trial NCT05240443: Bariatric Surgery and Chronic Renal Disease
Official title: Effect of Bariatric Surgery on Chronic Renal Disease (BARICADE): A Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Bariatric Surgery
Chronic Kidney Diseases
Obesity
Keywords: Bariatric Surgery
Chronic Kidney Disease
Obesity
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: American College of Surgeons
name: McMaster Surgical Associates
First posted: 2022-02-15
Enrollment: 60
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: Single-centre, open-label, parallel-arm feasibility randomized controlled trial with blinded endpoint assessment.
Primary purpose: TREATMENT

Brief summary: Obesity can be a major driver for the development of chronic kidney disease (CKD), which is a leading cause of death and significant loss in quality of life. A growing body of evidence has shown bariatric (metabolic) surgery as a novel approach to reduce the progression of CKD and reduce morbidity with sustained weight loss. This pilot trial will inform the design and execution of a large RCT that could determine the efficacy of bariatric surgery in the treatment of patients with CKD in the context of obesity. Ultimately, the results have the potential to influence guidelines that may deem bariatric surgery as a viable treatment option for CKD and reduce the morbidity from this chronic condition and inform clinical practice.

Detailed description: Obesity is a major driver for the development of CKD, which is a leading cause of death and greatly reduces one's quality of life. With a global prevalence of 9.1% (7.2% in Canada), CKD affects an estimated 13.6% of the American population and was associated with over $50 billion in healthcare costs, with an additional $30 billion in costs associated with end-stage renal disease (ESRD). Moreover, with an aging Canadian population, the prevalence of CKD is expected to rise over the coming years with patients progressing to higher disease burdens. This, in part, has led to a substantial increase in renal replacement therapy by means of dialysis or kidney transplant by 43.1% since 1990. Obesity is also an important modulatory factor in the development of poor outcomes as a result of CKD and has been linked to an increased rate of progression from CKD towards kidney failure. The most common comorbidities in patients with CKD were hypertension, diabetes, heart failure, chronic pulmonary disease, and atrial fibrillation and in Canada, 25% of patients with CKD have at least 3 or more comorbidities which too are associated with an increased risk of hospitalization and early death. Most worryingly, unlike other non-communicable diseases today, the age-standardized mortality for CKD has not declined over the past decades. Therefore, innovative strategies are of timely importance to reduce mortality and morbidity in patients with CKD and thus urgently needed, especially in patients with multiple comorbidities and targeting weight loss is a promising avenue to find novel treatment options.

Bariatric surgery has been shown to not only facilitate sustained weight loss in patients with obesity, but also independently improve cardiac risk factors such as dyslipidemia, hypertension, and type 2 diabetes mellitus. It has also been shown to reverse glomerular hyperfiltration and lower proteinuria in patients with obesity and normal kidney function and delay the need for renal transplantation in patients with ESRD. Moreover, the protective benefit of bariatric surgery has been shown to reduce risk of CKD progression for up to seven years after intervention in observational studies. However, current guidelines do not address a role for bariatric surgery in the management of patients with obesity and CKD.

Given the poor outcomes with patients with obesity and CKD, a RCT to assess the efficacy and safety of bariatric surgery as an intervention for patients with CKD is of timely importance. The present proposed pilot RCT of bariatric surgery versus medical management alone for patients with morbid obesity and CKD in order to assess whether a large, multi-centre, efficacy trial is feasible. The results of the proposed pilot study will thus inform the design of a larger RCT in this patient population.

Eligibility criteria: Inclusion Criteria:

* Patient age \>18
* Body mass index \> 40 (or \> 35 kg/m2 for patients with comorbidities)
* Diagnosis of CKD stage III (G3a or A2) defined as the presence of any of the following:

  1. glomerular filtration rate (GFR) under 60 mL/min/1.73 m2 as estimated from serum creatinine or cystatin C with the CKD-EPI equation
  2. ACR \> 30 mg/g
* Patient is deemed eligible to undergo bariatric surgery according to Ontario Bariatric Network (OBN) guidelines \[contradictions to OBN guidelines include non-Ontario resident, age \>70 years, history of cancer \<2 years, current substance use disorder, accessed palliative care, previous organ transplant (liver, heart, or lungs), active cardiac disease, major revascularization procedures within 6 months, or severe liver disease with ascites \<1 year\]

Exclusion Criteria:

* Hospital admission for kidney failure or acute kidney injury within 30 days of enrollment
* Documented GFR \> 60 mL/min/1.73 m2 or ACR \< 30 mg/g within 30 days of enrollment
* Documented confounders of kidney function measurement such as urinary tract infection or use of creatinine elevating medications or use of medications which interfere with measurement
* Contradiction to OBN guidelines including non-Ontario resident, age \>70 years, history of cancer \<2 years, current substance use disorder, accessed palliative care, previous organ transplant (liver, heart, or lungs), active cardiac disease, major revascularization procedures within 6 months, or severe liver disease with ascites \<1 year
* Life expectancy \<2 years due to non-CKD causes OR Untreated or inadequately treated psychiatric illness OR Risk of general anesthesia deemed too excessive OR Inability to provide informed consent

Primary outcomes:
measure: Estimated Glomerular Filtration Rate (units: ml/min/1.73m2) at 6 months
timeFrame: Month 6
measure: Estimated Glomerular Filtration Rate (units: ml/min/1.73m2) at 12 months
timeFrame: Month 12
measure: Estimated Glomerular Filtration Rate (units: ml/min/1.73m2) at 18 months
timeFrame: Month 18
measure: Measured Glomerular Filtration Rate (units: ml/min/1.73m2) at 6 months
timeFrame: Month 6
measure: Measured Glomerular Filtration Rate (units: ml/min/1.73m2) at 12 months
timeFrame: Month 12
measure: Measured Glomerular Filtration Rate (units: ml/min/1.73m2) at 18 months
timeFrame: Month 18
measure: Creatine Clearance (units: mL/min) at 6 months
timeFrame: Month 6
measure: Creatine Clearance (units: mL/min) at 12 months
timeFrame: Month 12
measure: Creatine Clearance (units: mL/min) at 18 months
timeFrame: Month 18
measure: Serum Creatinine (units: μmol/L) at 6 months
timeFrame: Month 6
measure: Serum Creatinine (units: μmol/L) at 12 months
timeFrame: Month 12
measure: Serum Creatinine (units: μmol/L) at 18 months
timeFrame: Month 18
measure: Serum Cystatin C (units: mg/L) at 6 months
timeFrame: Month 6
measure: Serum Cystatin C (units: mg/L) at 12 months
timeFrame: Month 12
measure: Serum Cystatin C (units: mg/L) at 18 months
timeFrame: Month 18
measure: Urine Albumin-Creatine Ratio (units: mg/g) at 6 months
timeFrame: Month 6
measure: Urine Albumin-Creatine Ratio (units: mg/g) at 12 months
timeFrame: Month 12
measure: Urine Albumin-Creatine Ratio (units: mg/g) at 18 months
timeFrame: Month 18
Secondary outcomes:
measure: Weight and height will be combined to report BMI in kg/m^2 at 6 months
timeFrame: Month 6
measure: Weight and height will be combined to report BMI in kg/m^2 at 12 months
timeFrame: Month 12
measure: Weight and height will be combined to report BMI in kg/m^2 at 18 months
timeFrame: Month 18
measure: Recruitment Rate (60 patients will be recruited at an average recruitment rate of 1.25 patients per site per month.)
timeFrame: Month 6
measure: Intervention Administration Rate
timeFrame: Month 6
measure: Crossover rate between control and intervention arm
timeFrame: Month 6
measure: Number of patients adhering to study treatments
timeFrame: Month 6
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
Study officials:
affiliation: McMaster University
name: Dennis Hong, MD MSc FRCSC
role: PRINCIPAL_INVESTIGATOR
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