BARICADE: Bariatric Surgery and Chronic Renal Disease

Sponsor

McMaster University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05240443

Collaborator

American College of Surgeons (Other), McMaster Surgical Associates (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

4.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bariatric Surgery Chronic Kidney Diseases Obesity	Procedure: Bariatric Surgery + Medical Management of CKD. Other: Medical Management for CKD	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Single-centre, open-label, parallel-arm feasibility randomized controlled trial with blinded endpoint assessment.Single-centre, open-label, parallel-arm feasibility randomized controlled trial with blinded endpoint assessment.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Effect of Bariatric Surgery on Chronic Renal Disease (BARICADE): A Pilot Randomized Controlled Trial

Anticipated Study Start Date :

Apr 1, 2022

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bariatric Surgery + Medical Management for Chronic Kidney Disease The intervention group will include medical management and bariatric surgery, which will consist of Roux-en-Y gastric bypass or sleeve gastrectomy performed according to local practice standards. Medical management for CKD will be directed by nephrologists at St. Joseph's Healthcare Hamilton. Comorbidities such as hypertension, dyslipidemia, and type 2 diabetes will be managed at the discretion of individual nephrologists. Generally, this can include anti-hypertensives (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) for systolic blood pressure control below a target of <140/90 mmHg (<130/80 in patients with type 2 diabetes), statins in patients with dyslipidemia to target low-density lipoprotein <2mmol/L for the treatment of CKD.	Procedure: Bariatric Surgery + Medical Management of CKD. The intervention group will include medical management and bariatric surgery, which will consist of Roux-en-Y gastric bypass or sleeve gastrectomy performed according to local practice standards. Medical management for CKD will be directed by nephrologists at St. Joseph's Healthcare Hamilton. Comorbidities such as hypertension, dyslipidemia, and type 2 diabetes will be managed at the discretion of individual nephrologists. Generally, this can include anti-hypertensives (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) for systolic blood pressure control below a target of <140/90 mmHg (<130/80 in patients with type 2 diabetes), statins in patients with dyslipidemia to target low-density lipoprotein <2mmol/L for the treatment of CKD.
Active Comparator: Medical Management for Chronic Kidney Disease Medical management for CKD will be directed by nephrologists at St. Joseph's Healthcare Hamilton. Comorbidities such as hypertension, dyslipidemia, and type 2 diabetes will be managed at the discretion of individual nephrologists. Generally, this can include anti-hypertensives (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) for systolic blood pressure control below a target of <140/90 mmHg (<130/80 in patients with type 2 diabetes), statins in patients with dyslipidemia to target low-density lipoprotein <2mmol/L for the treatment of CKD.	Other: Medical Management for CKD Medical management for CKD will be directed by nephrologists at St. Joseph's Healthcare Hamilton. Comorbidities such as hypertension, dyslipidemia, and type 2 diabetes will be managed at the discretion of individual nephrologists. Generally, this can include anti-hypertensives (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) for systolic blood pressure control below a target of <140/90 mmHg (<130/80 in patients with type 2 diabetes), statins in patients with dyslipidemia to target low-density lipoprotein <2mmol/L for the treatment of CKD.

Arm

Intervention/Treatment

Experimental: Bariatric Surgery + Medical Management for Chronic Kidney Disease

The intervention group will include medical management and bariatric surgery, which will consist of Roux-en-Y gastric bypass or sleeve gastrectomy performed according to local practice standards. Medical management for CKD will be directed by nephrologists at St. Joseph's Healthcare Hamilton. Comorbidities such as hypertension, dyslipidemia, and type 2 diabetes will be managed at the discretion of individual nephrologists. Generally, this can include anti-hypertensives (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) for systolic blood pressure control below a target of <140/90 mmHg (<130/80 in patients with type 2 diabetes), statins in patients with dyslipidemia to target low-density lipoprotein <2mmol/L for the treatment of CKD.

Procedure: Bariatric Surgery + Medical Management of CKD.

Active Comparator: Medical Management for Chronic Kidney Disease

Medical management for CKD will be directed by nephrologists at St. Joseph's Healthcare Hamilton. Comorbidities such as hypertension, dyslipidemia, and type 2 diabetes will be managed at the discretion of individual nephrologists. Generally, this can include anti-hypertensives (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) for systolic blood pressure control below a target of <140/90 mmHg (<130/80 in patients with type 2 diabetes), statins in patients with dyslipidemia to target low-density lipoprotein <2mmol/L for the treatment of CKD.

Other: Medical Management for CKD

Outcome Measures

Primary Outcome Measures

Estimated Glomerular Filtration Rate (units: ml/min/1.73m2) at 6 months [Month 6]
Estimated Glomerular Filtration Rate (units: ml/min/1.73m2) at 12 months [Month 12]
Estimated Glomerular Filtration Rate (units: ml/min/1.73m2) at 18 months [Month 18]
Measured Glomerular Filtration Rate (units: ml/min/1.73m2) at 6 months [Month 6]
Measured Glomerular Filtration Rate (units: ml/min/1.73m2) at 12 months [Month 12]
Measured Glomerular Filtration Rate (units: ml/min/1.73m2) at 18 months [Month 18]
Creatine Clearance (units: mL/min) at 6 months [Month 6]
Creatine Clearance (units: mL/min) at 12 months [Month 12]
Creatine Clearance (units: mL/min) at 18 months [Month 18]
Serum Creatinine (units: μmol/L) at 6 months [Month 6]
Serum Creatinine (units: μmol/L) at 12 months [Month 12]
Serum Creatinine (units: μmol/L) at 18 months [Month 18]
Serum Cystatin C (units: mg/L) at 6 months [Month 6]
Serum Cystatin C (units: mg/L) at 12 months [Month 12]
Serum Cystatin C (units: mg/L) at 18 months [Month 18]
Urine Albumin-Creatine Ratio (units: mg/g) at 6 months [Month 6]
Urine Albumin-Creatine Ratio (units: mg/g) at 12 months [Month 12]
Urine Albumin-Creatine Ratio (units: mg/g) at 18 months [Month 18]

Secondary Outcome Measures

Weight and height will be combined to report BMI in kg/m^2 at 6 months [Month 6]
Weight and height will be combined to report BMI in kg/m^2 at 12 months [Month 12]
Weight and height will be combined to report BMI in kg/m^2 at 18 months [Month 18]
Recruitment Rate (60 patients will be recruited at an average recruitment rate of 1.25 patients per site per month.) [Month 6]
60 patients will be recruited at an average recruitment rate of 1.25 patients per site per month.
Intervention Administration Rate [Month 6]
>80% of patients randomized to the intervention arm will undergo bariatric surgery within 30 days of randomization.
Crossover rate between control and intervention arm [Month 6]
Number of patients adhering to study treatments [Month 6]
Patients will be monitored and asked about adherence at follow-ups.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

glomerular filtration rate (GFR) under 60 mL/min/1.73 m2 as estimated from serum creatinine or cystatin C with the CKD-EPI equation
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