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

Sponsor

Ain Shams University (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT05577507

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

39.9

Patients Per Site Per Month

Study Details

Study Description

Brief 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

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Diseases Hemodialysis Complication Hyperphosphatemia	Drug: Cholestyramine Resin 4000 MG [Questran] Drug: Calcium Carbonate 500 MG Oral Tablet	Phase 4

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.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

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)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

Official Title:

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

Anticipated Study Start Date :

Mar 30, 2023

Anticipated Primary Completion Date :

May 30, 2023

Anticipated Study Completion Date :

May 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Test group 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] cholestyramine 4 gram sachets (questran) will be administered orally on 150 ml water three times daily for 8 weeks period trial Drug: Calcium Carbonate 500 MG Oral Tablet control group will administer standard therapy calcium carobonate as calcium based phosphate binder 500 mg three times daily within meals
Placebo Comparator: Control group Group 2: Control group, 40 patients will take only the standard therapy calcium-based phosphate binder (Calcimate).	Drug: Calcium Carbonate 500 MG Oral Tablet control group will administer standard therapy calcium carobonate as calcium based phosphate binder 500 mg three times daily within meals

Arm

Intervention/Treatment

Active Comparator: Test group

Drug: Cholestyramine Resin 4000 MG [Questran]

cholestyramine 4 gram sachets (questran) will be administered orally on 150 ml water three times daily for 8 weeks period trial

Drug: Calcium Carbonate 500 MG Oral Tablet

control group will administer standard therapy calcium carobonate as calcium based phosphate binder 500 mg three times daily within meals

Placebo Comparator: Control group

Group 2: Control group, 40 patients will take only the standard therapy calcium-based phosphate binder (Calcimate).

Drug: Calcium Carbonate 500 MG Oral Tablet

control group will administer standard therapy calcium carobonate as calcium based phosphate binder 500 mg three times daily within meals

Outcome Measures

Primary Outcome Measures

serum phosphate level [8 weeks trial period]
measuring serum phosphate level at baseline and after 8 weeks trial period to evaluate serum phosphate reduction by cholestyramine
serum calcium level [8 weeks trial period]
measuring serum calcium level at baseline and after 8 weeks trial period to evaluate serum calcium reduction by cholestyramine
iPTH [8 weeks trial period]
measuring iPTH level at baseline and after 8 weeks trial period to evaluate iPTH reduction by cholestyramine

Secondary Outcome Measures

Lipid Profile ( triglyceride level , LDL ,HDL ,Total cholesterol ) [8 weeks trial period]
measuring LDL , total cholesterol reduction after using cholestyramine for 8 weeks trial period

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)