Efficacy and Safety of Cholestyramine in the Management of Hyperphosphatemia in Adult Hemodialysis Patients
Condition: Chronic Kidney Diseases; Hemodialysis Complication; Hyperphosphatemia
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Hyperphosphatemia
Study type: Interventional
Phase: Phase 4

Summary: 
      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

        1. Age, sex, weight, duration of ESRD and hemodialysis comorbidities.

        2. 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: 
      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

        1. Age, sex, weight, duration of ESRD and hemodialysis comorbidities.

        2. 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
    

Intervention name(s): Cholestyramine Resin 4000 MG [Questran]; Calcium Carbonate 500 MG Oral Tablet
Intervention type(s): Drug; Drug
Intervention description(s): cholestyramine 4 gram sachets (questran) will be administered orally on 150 ml water three times daily for 8 weeks period trial; control group will administer standard therapy calcium carobonate as calcium based phosphate binder 500 mg three times daily within meals
Intervention MeSH terms: Calcium Carbonate; Cholestyramine Resin; Calcium
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention 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)
Primary purpose: Treatment
Keywords: chronic kidney disease; hyperphosphatemia in chronic adult hemodialysis patients; bile acid sequestrants: cholestyramine; serum calcium level, serum phosphate level