Sevelamer Hydrochloride and Femoral and Carotid Intima Media Thickness Progression in End Stage Renal Disease (SUMMER)

A Randomized-controlled Trial Comparing the Efficacy of Two Phosphorous Binders, Renagel and Caltrate in Reducing the Rate of Progression of Femoral and Carotid IMT Thickening as Measured by B-mode Ultrasound in Dialysis Patients.

Aims of the multi-center, randomized, treatment-controlled clinical trial are to compare the efficacy of sevelamer hydrochloride to calcium-containing phosphorus binders in reducing the rate of progression of femoral and carotid intimal media thickness (IMT) thickening as measured by B-mode ultrasound in stable maintenance hemodialysis (HD) patients.

Study Overview

• Status: Completed
• Conditions: Hemodialysis; End Stage Renal Disease; Intimal Media Thickness
• Intervention / Treatment: Drug: sevelamer hydrochloride; Drug: Calcium Carbonate

Detailed Description

Serum phosphorus (P) is frequently elevated in HD patients. Serum P stimulates PTH synthesis and is associated with secondary hyperparathyroidism. Use of calcium(Ca)-containing phosphorus-binders is an exogenous source of Ca that can elevate the CaxP product. In HD patients, an ultrasonographically-demonstrated increase in intima media thickness of the carotid artery has been associated with elevated serum P levels.Peripheral arterial vascular disease (PVD) accounts for significant mortality and morbidity in HD patients.

The aim of this study is to compare the efficacy of sevelamer hydrochloride to calcium-containing phosphorus binders in reducing the rate of progression of femoral and carotid intimal media thickness (IMT) thickening as measured by B-mode ultrasound in stable HD patients.

Subject randomization numbers was provided by the Epidemiology and Research Unit, E. Wolfson Medical Center, Holon, Israel. After meeting all inclusion criteria, subjects were randomized to one of two treatment groups: Renagel or calcium carbonate. Prior to receiving treatment, baseline femoral and carotid IMT were measured, medical and pharmaceutical history was documented, nutrition assessment was undertaken and midweek blood chemistry and blood count were measured. No change in patient medication prescription was required during this study, with the exception of phosphorus binders. All other concomitant medications were continued. During the year of the study, routine monthly blood tests were obtained for chemistry, blood count, and PTH was measured once every 4 months.

After a year of treatment, femoral and carotid IMT were measured again, midweek blood chemistry and blood count were measured.

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Holon, Israel
    • Edith Wolfson Medical Center
  • Tel Aviv, Israel
    • Tel Aviv Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HD Patients aged 40-75 years inclusive if they received HD treatment three times each week for not less than three months, and if they had not been treated with sevelamer hydrochloride. Patients of both genders, without regard to diabetes status, history of CVD or underlying renal disease were eligible.

Exclusion Criteria:

• Patients receiving treatment with sevelamer hydrochloride were not eligible for study participation. Additionally, patients were excluded if they had active liver disease, known sensitivity to either sevelamer hydrochloride or calcum carbonate or if their participation in the study was deemed in any way detrimental or unwarranted by the patient's treating physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sevelamer hydrochloride	Drug: sevelamer hydrochloride; 800-3200 mg with each meal; Other Names: Renagel
ACTIVE_COMPARATOR: Calcium carbonate	Drug: Calcium Carbonate; 600 mg with each meal, up to 1800 mg a day; Other Names: Caltrate, Calcimor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Increase in carotid and femoral IMT as measured using B-mode ultrasonography	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Clinically evident PVD in a previously unaffected limb confirmed by doppler or duplex ultrasonography. Also, serum P, serum Ca, PTH and % of treatment group compliant with the revised treatment goals .	1 year

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center
• Collaborators: Genzyme, a Sanofi Company; Wolfson Medical Center
• Investigators: Principal Investigator: Talia Weinstein, MD PhD, Tel Aviv Medical Center; Principal Investigator: Mona Boaz, PhD, Edith Wolfson Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (ACTUAL): February 1, 2009
• Study Completion (ACTUAL): February 1, 2009

Study Registration Dates

• First Submitted: January 13, 2010
• First Submitted That Met QC Criteria: January 13, 2010
• First Posted (ESTIMATE): January 14, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): January 14, 2010
• Last Update Submitted That Met QC Criteria: January 13, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Keywords: hemodialysis; intimal media thickness
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Calcium-Regulating Hormones and Agents; Chelating Agents; Sequestering Agents; Antacids; Calcium; Sevelamer; Calcium Carbonate
• Other Study ID Numbers: 04-285