Efficacy and Safety of Cholestyramine in the Management of Hyperphosphatemia in Adult Hemodialysis Patients

Study Overview
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Brief Summary
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The aim of the study is to evaluate the efficacy and safety of cholestyramine in the management of hyperphosphatemia in hemodialysis patients. Colestilan is a non-metallic phosphate binder that acts as an anion-exchange resin. Colestilan itself is not absorbed after oral administration, and it is able to bind dietary phosphate within the gastrointestinal tract and thus prevent absorption of the mineral. Initial, Phase II, studies showed that it reduces serum phosphorus levels in dialysis patients with hyperphosphatemia without affecting serum calcium levels. There are no studies conducted about the feasibility and efficacy of cholestyramine as an oral phosphate binder in hemodialysis patients. Relying on the efficacy and safety of bile acid sequestrants such as colestilan and colestipol in the management of hyperphosphatemia and hypercholesterolemia in hemodialysis patients, cholestyramine is selected to be studied in hemodialysis patients. A total of 80 patients will be recruited and divided into 2 groups: - Group 1: (cholestyramine 12 gram), 40 patients will take a dose of cholestyramine 4-gram sachet in 150-200 ml water or juice three times daily within meals as an add on therapy with standard therapy calcium-based phosphate binder (Calcimate). Group 2: Control group, 40 patients will take only the standard therapy calcium-based phosphate binder (Calcimate). Time of the trial will be two months (8 weeks trial period) Baseline characteristics: The following data will be collected from all patients at baseline Age, sex, weight, duration of ESRD and hemodialysis comorbidities. Dialysis duration, serum phosphate level, serum calcium level, iPTH, BUN, Cr (mg/d L), Albumin (mg/d L), Hb (g m%), renal function test, liver function test, blood glucose level, TG, total cholesterol level, LDL-C, HDL.C. After the end of trial, we will examine if cholestyramine has a significant efficacy on reducing serum phosphate level in adult hemodialysis patients.

Detailed Description
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Chronic kidney disease-mineral and bone disorder (CKD-MBD) is characterized by progressive loss of renal function as well as dysregulation of mineral and bone metabolism, leading frequently to hyperphosphatemia. Multiple studies have consistently shown that hyperphosphatemia is associated with cardiovascular events and increased morbidity and mortality in end-stage renal disease (ESRD) patients. Importantly, use of phosphate binding agents and reduction of serum phosphate concentration are associated with a lower risk of mortality. The most widely used phosphate binders are calcium-based, although they are frequently associated with hypercalcemia and vascular calcification. Bile acid sequestrates like colestipol, colestilan and cholestyramine are pharmacologic molecules that bind to bile acids in the intestine resulting in the interruption of bile acid homeostasis and, consequently, reduction in low-density lipoprotein cholesterol levels in hypercholesterolemia. Colestilan is a non-metallic phosphate binder that acts as an anion-exchange resin. Colestilan itself is not absorbed after oral administration, and it is able to bind dietary phosphate within the gastrointestinal tract and thus prevent absorption of the mineral. Initial, Phase II, studies showed that it reduces serum phosphorus levels in dialysis patients with hyperphosphatemia without affecting serum calcium levels. There are no studies conducted about the feasibility and efficacy of cholestyramine as an oral phosphate binder in hemodialysis patients. Relying on the efficacy and safety of bile acid sequestrants such as colestilan and colestipol in the management of hyperphosphatemia and hypercholesterolemia in hemodialysis patients, cholestyramine is selected to be studied in hemodialysis patients. The aim of the study is to evaluate the efficacy and safety of cholestyramine in the management of hyperphosphatemia in hemodialysis patients. A total of 80 patients will be recruited and divided into 2 groups: - Group 1: (cholestyramine 12 gram), 40 patients will take a dose of cholestyramine 4-gram sachet in 150-200 ml water or juice three times daily within meals as an add-on therapy with standard therapy calcium-based phosphate binder (Calcimate). Group 2: Control group, 40 patients will take only the standard therapy calcium-based phosphate binder (Calcimate). Time of the trial will be two months (8 weeks trial period) Baseline characteristics: The following data will be collected from all patients at baseline Age, sex, weight, duration of ESRD and hemodialysis comorbidities. Dialysis duration, serum phosphate level, serum calcium level, iPTH, BUN, Cr (mg/d L), Albumin (mg/d L), Hb (g m%), renal function test, liver function test, blood glucose level, TG, total cholesterol level, LDL-C, HDL.C. After the end of trial, we will examine if cholestyramine has a significant efficacy on reducing serum phosphate level in adult hemodialysis patients. Parameters will be collected from all patients after 8-week trial period: Serum phosphate, serum calcium, iPTH, LDL, TG and total cholesterol level

Official Title
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Efficacy and Safety of Cholestyramine in the Management of Hyperphosphatemia in Adult Hemodialysis Patients

Conditions
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Chronic Kidney Diseases, Hemodialysis Complication, Hyperphosphatemia

Intervention / Treatment
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* Drug: Cholestyramine Resin 4000 MG [Questran]
* Drug: Calcium Carbonate 500 MG Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Patients aged ≥18 years with CKD stage (4&5) Serum phosphate level ≥ 5.5 mg/dL Serum LDL-C level ≥1.82 mmol/L (70 mg/dL) Hemodialysis frequency 3 times per week or more. Hemodialysis in the last 3 months or longer. Exclusion Criteria: Patients are excluded if they have a history of clinically significant gastrointestinal motility disorder, dysphagia, or swallowing disorder. 2-patients require warfarin or digoxin treatment. 3- Patients have a history of alcohol or substance abuse 4- Patients receiving calcimimetics. 5- Pregnant patients or patients planning pregnancy. 6- Patients have Triglyceride level above 300 (mg/dl)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A total of 80 patients will be recruited and divided into 2 groups: - Group 1: (cholestyramine 12 gram), 40 patients will take a dose of cholestyramine 4-gram sachet in 150-200 ml water or juice three times daily within meals as an add-on therapy with standard therapy calcium-based phosphate binder (Calcimate). Group 2: Control group, 40 patients will take only the standard therapy calcium-based phosphate binder (Calcimate). Time of the trial will be two months (8 weeks trial period)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Test group<br>Group 1: (cholestyramine 12 gram), 40 patients will take a dose of cholestyramine 4-gram sachet in 150-200 ml water or juice three times daily within meals as an add-on therapy with standard therapy calcium-based phosphate binder (Calcimate). Dosage: one sachet on 150 ml water three times daily duration : 8 weeks | Drug: Cholestyramine Resin 4000 MG [Questran]<br>* cholestyramine 4 gram sachets (questran) will be administered orally on 150 ml water three times daily for 8 weeks period trial<br>Drug: Calcium Carbonate 500 MG Oral Tablet<br>* control group will administer standard therapy calcium carobonate as calcium based phosphate binder 500 mg three times daily within meals<br>|
| Placebo Comparator: Control group<br>Group 2: Control group, 40 patients will take only the standard therapy calcium-based phosphate binder (Calcimate). | Drug: Calcium Carbonate 500 MG Oral Tablet<br>* control group will administer standard therapy calcium carobonate as calcium based phosphate binder 500 mg three times daily within meals<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum phosphate level | measuring serum phosphate level at baseline and after 8 weeks trial period to evaluate serum phosphate reduction by cholestyramine | 8 weeks trial period | 
| serum calcium level | measuring serum calcium level at baseline and after 8 weeks trial period to evaluate serum calcium reduction by cholestyramine | 8 weeks trial period | 
| iPTH | measuring iPTH level at baseline and after 8 weeks trial period to evaluate iPTH reduction by cholestyramine | 8 weeks trial period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lipid Profile ( triglyceride level , LDL ,HDL ,Total cholesterol ) | measuring LDL , total cholesterol reduction after using cholestyramine for 8 weeks trial period | 8 weeks trial period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic kidney disease, hyperphosphatemia in chronic adult hemodialysis patients, bile acid sequestrants: cholestyramine, serum calcium level, serum phosphate level