Arterial Stiffness and Calcifications in Haemodialysis Patients on Sevelamer or Calcium Acetate

NCT00364000 | Withdrawn DMC

• 1 other identifier: 02_2006
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

End-stage renal disease (ESRD) is a state of increased arterial stiffness of extensive vessel calcifications, compared with the non-renal population. Both arterial stiffness and arterial calcifications are potent predictors of all-cause and cardiovascular mortality in ESRD patients. Several studies have documented the direct relationship between the extent and severity of arterial/coronary calcifications and outcome in dialysis patients. The relationship is strong no matter if arterial calcifications were quantified by electron-beam computed tomography or a radiological calcification score. Calcifications are early and progressive events in these patients. PWV is strongly related to the degree of sonographic determined arterial calcifications and EBCT-derived coronary artery calcium score in chronic kidney disease patients. Calcium-based phosphate binders are associated with progressive coronary artery and aortic calcification, especially when mineral metabolism is not well controlled. According to recent studies, sevelamer hydrochloride is a potent non-calcium-containing phosphate binder, well tolerated in ESRD. Compared with calcium-based phosphate binders, sevelamer is less likely to cause hypercalcemia, low levels of PTH, and progressive coronary and aortic calcification in hemodialysis patients. Moreover, sevelamer has a favorable effect on the lipid profile. Less is known about the relationship between sevelamer treatment and progression of arterial stiffness. To date, there is one single study examining the influence of sevelamer (versus calcium carbonate) on the evolution of arterial stiffness in a very small number (N=15) of haemodialysis patients. These study used the same patients as historical controls, thus being methodologically rather weak. Moreover, the follow-up was quite short - 6 month. The aim of the trial is to to quantify, in a randomized opened-labeled controlled trial the effect of sevelamer hydrochloride on the evolution of arterial stiffness parameters (pulse wave velocity and the augmentation index) in chronic haemodialysis patients and to correlate these parameters with arterial calcification assessed by a previous described radiological score of arterial calcification and echocardiographic parameters (left ventricular hypertrophy, LV dilatation, systolic and diastolic dysfunction).

Conditions

Haemodialyzed Patients; Hyperphosphatemia

Keywords

haemodialysis; hyperphosphatemia; sevelamer; calcium acetate

Outcome Measures

Primary Outcomes (2)

• changes in arterial stiffness parameters

  6 months

• changes in calcification score

  6 months

Secondary Outcomes (1)

• composite of all-cause mortality, cardiovascular mortality and major cardiovascular events

  1 year

Study Arms (2)

I

ACTIVE COMPARATOR

Calcium acetate 670 mg tablets

Drug: Calcium acetate

II

EXPERIMENTAL

label sevelamer (RenagelR) 800 mg tablets

Drug: Calcium acetate; Drug: Sevelamer

Interventions

Calcium acetate DRUG

Calcium acetate in 240 chronic HD patients

I; II

Sevelamer DRUG

label sevelamer (RenagelR) 800 mg tablets

II

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• more than 3 months on haemodialysis
• willingness to participate
• age 18-60 yrs
• pre-dialysis blood pressure 120-160 mmHg in the last month prior to the initiation of study or recent (\<1 Mo) addition of a new antihypertensive drug
• iPTH at entry 200-800 pg/mL (as per severe hyperparathyroidism)
• serum calcium at entry 2.2-2.6 mmol/L

You may not qualify if:

• haemodynamic instability
• uncontrolled hypertension
• any severe, debilitating disease associated with a reduced survival
• any major cardiovascular event in the last 12 month before study
• cinacalcet therapy before study entrance
• history of parathyroidectomy
• documented history of poor compliance
• serious gastrointestinal disease

Sponsors & Collaborators

• Romanian Society of Nephrology: lead

Study Sites (2)

"Dr Carol Davila" Teaching Hospital of Nephrology

Bucharest, 010731, Romania

Location

"CI Parhon" Clinical Hospital

Iași, Romania

Location

Related Publications (1)

• Natale P, Green SC, Ruospo M, Craig JC, Vecchio M, Elder GJ, Strippoli GF. Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD). Cochrane Database Syst Rev. 2025 Jun 27;6(6):CD006023. doi: 10.1002/14651858.CD006023.pub4.

  PMID: 40576086 DERIVED

MeSH Terms

Conditions

Hyperphosphatemia

Interventions

calcium acetate; Sevelamer

Condition Hierarchy (Ancestors)

Phosphorus Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Polyamines; Amines; Organic Chemicals

Study Officials

• Adrian Covic, Prof

  "CI Parhon" Clinical Hospital, Iasi

  STUDY DIRECTOR

• Gabriel Mircescu, Prof

  "Dr Carol Davila" Teaching Hospital of Nephrology, Bucharest, Romania

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD. PHD

Study Record Dates

• First Submitted: August 10, 2006
• First Posted: August 15, 2006
• Study Start: January 1, 2012
• Primary Completion: July 1, 2015
• Study Completion: December 1, 2017
• Last Updated: December 22, 2017

Record last verified: 2017-12

Locations

RO (2)