Reduce Cardiovascular Calcifications to Reduce QT Interval in Dialysis - Full Text View

Sponsored by:	Azienda Sanitaria ASL Avellino 2
Information provided by:	Azienda Sanitaria ASL Avellino 2
ClinicalTrials.gov Identifier:	NCT00710788

Purpose

Research proposal to evaluate the impact of different phosphate binders on the progression of cardiovascular calcification and QT dispersion in new haemodialysis patients.

Condition	Intervention
Cardiovascular Mortality	Drug: sevelamer phosphate-binders Drug: Ca-carbonate, Ca-acetate, Aluminium

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety Study
Official Title:	Interventional, Multicenter, Prospective, Randomized Trial to Slow Down the Progression of Cardiovascular Calcifications to Reduce QTd in Incident Dialysis Patients

Resource links provided by NLM:

Genetics Home Reference related topics: short QT syndrome

Drug Information available for: Sevelamer Sevelamer hydrochloride Sevelamer carbonate Aluminum

U.S. FDA Resources

Further study details as provided by Azienda Sanitaria ASL Avellino 2:

Primary Outcome Measures:

death [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

QT interval [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	360
Study Start Date:	January 2008
Estimated Study Completion Date:	January 2010
Primary Completion Date:	January 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental sevelamer as Phosphate-binder treatment	Drug: sevelamer phosphate-binders 1600 mg/day for 2 years
2: Active Comparator Ca-carbonate, Ca-acetate, Aluminium	Drug: Ca-carbonate, Ca-acetate, Aluminium Ca-carbonate 1 g/day for 2 years Ca-acetate 1 g/day for 2 years Aluminum 2 cpr/day

Detailed Description:

The risk of developing cardiovascular diseases in patients on hemodialysis is higher than in general population.

Higher levels of serum phosphate are associated with adverse cardiovascular outcomes, especially in the setting of overt hyperphosphatemia. Given the biological importance of serum phosphorus, it is conceivable that also within the normal range values the higher serum phosphate levels may be associated with the worst outcome.

Several paper have shown that vascular calcifications in dialysis patients are associated with increased relative risk of death; it has also been demonstrated in uremic patients that vascular calcifications decrease arterial elasticity. We previously observed that vascular calcification directly correlate with QT interval (QTc) as well as QT dispersion (QTd) in dialysis. Also, QT correction (obtained by the correction of phosphoremia and dyslipidemia) can ameliorate the development of arrhythmia and sudden death. Aim of this study is to evaluate the relationship between vascular calcifications and both QTd increase and mortality in incident hemodialysis patients, and to investigate the efficacy of sevelamer to reduce vascular calcifications and QTd.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

incident patients on haemodialysis (CKD stage 5);
an informed consent will be provided at the study entry.

Exclusion Criteria:

congenital prolongation of QT segment syndrome;
QTc >440 ms; increased QTd;
bradycardia <50 bpm;
sintomatic arrhythmia or any other significant heart problems;
electrolyte unbalances (especially hypokalemia, hypomagnesemia, hypocalcemia);
abnormal liver function tests;
hypothyroidism.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00710788

Locations

Italy, Avellino
Nephrology Division
Solofra, Avellino, Italy, 83100

Sponsors and Collaborators

Azienda Sanitaria ASL Avellino 2

Investigators

Study Chair:	Biagio R Di Iorio, MD, PhD	ASL AV/2, Avellino, Italy
Principal Investigator:	Loreto Gesualdo, professor	Nephrology Division, Medical School, University of Foggia
Principal Investigator:	Filippo Aucella, MD	ASL FG, Italy
Principal Investigator:	Walter De Simone, MD	AO MOscati, Avellino, Italy
Principal Investigator:	Mario Migliorati, MD	Dialysis, Torre del Greco, Italy
Principal Investigator:	Domenico Santoro, MD	Nephrology Division, Medical School, University of Messina, Italy
Principal Investigator:	Pasquale Guastaferro, MD	Nephrology Division, ASL AV1, Sant'Angelo de Lomnardi, Italy
Principal Investigator:	Luigi Chiuchuilo, MD	Dialysis, Avellino, Italy
Principal Investigator:	Vincenzo Tedesco, MD	Dialysis, Montella, Italy

More Information

Additional Information:

ASL AV2

This link exits the ClinicalTrials.gov site

Publications:

Marangon N, Lindholm B, Stenvinkel P. Nonphosphate-Binding Effects of Sevelamer-Are They of Clinical Relevance? Semin Dial. 2008 Jun 19; [Epub ahead of print]

Di Iorio BR, Bortone S, Piscopo C, Grimaldi P, Cucciniello E, D'Avanzo E, Mondillo F, Cillo N, Bellizzi V. Cardiac vascular calcification and QT interval in ESRD patients: is there a link? Blood Purif. 2006;24(5-6):451-9. Epub 2006 Aug 25.

Di Iorio BR, D'Avanzo E, Piscopo C, Grimaldi P, Cucciniello E, Cillo N, Bellizzi V. Progression of vascular calcification increases QT interval in haemodialysis patients. Nephrol Dial Transplant. 2006 Dec;21(12):3609-10. Epub 2006 Jul 31. No abstract available.

Cozzolino M, Galassi A, Pasho S, Fallabrino G, Gallieni M, Brancaccio D. Preventive measures and new pharmacological approaches of calcium and phosphate disorders. Contrib Nephrol. 2008;161:234-9.

Nolan CR, McCarron DA. Lack of mortality benefit with sevelamer. Kidney Int. 2008 May;73(9):1093; author reply 1093-4. No abstract available.

Suki WN; for the DCOR Investigators. Response to 'Lack of mortality benefit with sevelamer' Kidney Int. 2008 May;73(9):1093-1094. No abstract available.

Wrong O, Harland C. Sevelamer. Nephrol Dial Transplant. 2008 Jun;23(6):2108; author reply 2101-2. Epub 2008 Apr 9. No abstract available.

Negri AL. [K-DOQI guidelines for calcium and phosphorus metabolism in chronic kidney disease: outcomes, compliance and new drugs for treatment] Nefrologia. 2007;27(6):670-3. Review. Spanish. No abstract available.

Hamida FB, Fatma LB, Barbouch S, Kaaroud H, Helal I, Hedri H, Abdallah TB, Maiz HB, Kheder A. Effect of sevelamer on mineral and lipid abnormalities in hemodialysis patients. Saudi J Kidney Dis Transpl. 2008 Mar;19(2):183-8.

St Peter WL, Liu J, Weinhandl E, Fan Q. A comparison of sevelamer and calcium-based phosphate binders on mortality, hospitalization, and morbidity in hemodialysis: a secondary analysis of the Dialysis Clinical Outcomes Revisited (DCOR) randomized trial using claims data. Am J Kidney Dis. 2008 Mar;51(3):445-54.

Winkelmayer WC, Tonelli M. Phosphate binder choice in dialysis patients: a call for evidence-based rather than marketing-based clinical practice. Am J Kidney Dis. 2008 Mar;51(3):362-5. No abstract available.

Mansour J, Shahapuni I, El Esper N, Fournier A. Block randomized trial evidencing lower mortality with sevelamer compared with calcium phosphate binder in incident dialysis patients. Kidney Int. 2008 Feb;73(4):510. No abstract available.

Ferreira A, Frazão JM, Monier-Faugere MC, Gil C, Galvao J, Oliveira C, Baldaia J, Rodrigues I, Santos C, Ribeiro S, Hoenger RM, Duggal A, Malluche HH; Sevelamer Study Group. Effects of sevelamer hydrochloride and calcium carbonate on renal osteodystrophy in hemodialysis patients. J Am Soc Nephrol. 2008 Feb;19(2):405-12. Epub 2008 Jan 16.

Suki WN; Dialysis Clinical Outcomes Revisited Investigators. Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients: results of a randomized clinical trial. J Ren Nutr. 2008 Jan;18(1):91-8.

Russo D, Miranda I, Ruocco C, Battaglia Y, Buonanno E, Manzi S, Russo L, Scafarto A, Andreucci VE. The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer. Kidney Int. 2007 Nov;72(10):1255-61. Epub 2007 Sep 5.

Suki WN, Zabaneh R, Cangiano JL, Reed J, Fischer D, Garrett L, Ling BN, Chasan-Taber S, Dillon MA, Blair AT, Burke SK. Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients. Kidney Int. 2007 Nov;72(9):1130-7. Epub 2007 Aug 29.

Di Iorio B, D'Avanzo E, Piscopo C, Cucciniello E, Bellizzi V: QT and phosphatemia: a novel sensitive marker of cardiovascolar risk for an old killer . 12th Assisi European Meeting on Cardionephrology, Cardionephrology 10, Nuova BIOS ed, 2008;23-26

Responsible Party:	ASL_AV2 ( Biagio Raffaele Di Iorio )
Study ID Numbers:	2008.1, 2008.1.brd.renagel
Study First Received:	July 2, 2008
Last Updated:	July 3, 2008
ClinicalTrials.gov Identifier:	NCT00710788 History of Changes
Health Authority:	Italy: Ethics Committee

Keywords provided by Azienda Sanitaria ASL Avellino 2:

QT interval
QT dispersion
arrhythmias
death
TC score

Study placed in the following topic categories:

Sevelamer
Death
Aluminum magnesium hydroxide
Disease Progression
Arrhythmias, Cardiac

ClinicalTrials.gov processed this record on September 11, 2009