Reduce Cardiovascular Calcifications to Reduce QT Interval in Dialysis

NCT ID: NCT00710788

Last Updated: 2013-02-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

360 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-01-31

Study Completion Date

2011-09-30

Brief Summary

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

Detailed Description

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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.

Conditions

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Cardiovascular Mortality

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

sevelamer as Phosphate-binder treatment

Group Type EXPERIMENTAL

sevelamer phosphate-binders

Intervention Type DRUG

1600 mg/day for 2 years

2

Calcium carbonate

Group Type ACTIVE_COMPARATOR

Calcium Carbonate

Intervention Type DRUG

Calcium carbonate 1 g/day for 2 years

Interventions

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sevelamer phosphate-binders

1600 mg/day for 2 years

Intervention Type DRUG

Calcium Carbonate

Calcium carbonate 1 g/day for 2 years

Intervention Type DRUG

Other Intervention Names

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Renagel

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Azienda Sanitaria ASL Avellino 2

OTHER

Sponsor Role lead

Responsible Party

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Dr Biagio Di Iorio

MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Biagio R Di Iorio, MD, PhD

Role: STUDY_CHAIR

ASL AV/2, Avellino, Italy

Loreto Gesualdo, professor

Role: PRINCIPAL_INVESTIGATOR

Nephrology Division, Medical School, University of Foggia

Filippo Aucella, MD

Role: PRINCIPAL_INVESTIGATOR

ASL FG, Italy

Walter De Simone, MD

Role: PRINCIPAL_INVESTIGATOR

AO MOscati, Avellino, Italy

Mario Migliorati, MD

Role: PRINCIPAL_INVESTIGATOR

Dialysis, Torre del Greco, Italy

Domenico Santoro, MD

Role: PRINCIPAL_INVESTIGATOR

Nephrology Division, Medical School, University of Messina, Italy

Pasquale Guastaferro, MD

Role: PRINCIPAL_INVESTIGATOR

Nephrology Division, ASL AV1, Sant'Angelo de Lomnardi, Italy

Luigi Chiuchuilo, MD

Role: PRINCIPAL_INVESTIGATOR

Dialysis, Avellino, Italy

Vincenzo Tedesco, MD

Role: PRINCIPAL_INVESTIGATOR

Dialysis, Montella, Italy

Locations

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Nephrology Division

Solofra, Avellino, Italy

Site Status

Countries

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Italy

References

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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

Reference Type BACKGROUND

Marangon N, Lindholm B, Stenvinkel P. Nonphosphate-binding effects of sevelamer--are they of clinical relevance? Semin Dial. 2008 Sep-Oct;21(5):385-9. doi: 10.1111/j.1525-139X.2008.00440.x. Epub 2008 Jun 19.

Reference Type RESULT
PMID: 18573137 (View on PubMed)

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. doi: 10.1159/000095362. Epub 2006 Aug 25.

Reference Type RESULT
PMID: 16940716 (View on PubMed)

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. doi: 10.1093/ndt/gfl417. Epub 2006 Jul 31. No abstract available.

Reference Type RESULT
PMID: 16880182 (View on PubMed)

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;161:234-239. doi: 10.1159/000130696.

Reference Type RESULT
PMID: 18451682 (View on PubMed)

Nolan CR, McCarron DA. Lack of mortality benefit with sevelamer. Kidney Int. 2008 May;73(9):1093; author reply 1093-4. doi: 10.1038/ki.2008.46. No abstract available.

Reference Type RESULT
PMID: 18414441 (View on PubMed)

Wrong O, Harland C. Sevelamer. Nephrol Dial Transplant. 2008 Jun;23(6):2108; author reply 2101-2. doi: 10.1093/ndt/gfn162. Epub 2008 Apr 9. No abstract available.

Reference Type RESULT
PMID: 18400812 (View on PubMed)

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. No abstract available. Spanish.

Reference Type RESULT
PMID: 18336094 (View on PubMed)

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.

Reference Type RESULT
PMID: 18310864 (View on PubMed)

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. doi: 10.1053/j.ajkd.2007.12.002.

Reference Type RESULT
PMID: 18295060 (View on PubMed)

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. doi: 10.1053/j.ajkd.2008.01.004. No abstract available.

Reference Type RESULT
PMID: 18295050 (View on PubMed)

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. doi: 10.1038/sj.ki.5002752. No abstract available.

Reference Type RESULT
PMID: 18235525 (View on PubMed)

Ferreira A, Frazao 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. doi: 10.1681/ASN.2006101089. Epub 2008 Jan 16.

Reference Type RESULT
PMID: 18199805 (View on PubMed)

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. doi: 10.1053/j.jrn.2007.10.019.

Reference Type RESULT
PMID: 18089452 (View on PubMed)

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. doi: 10.1038/sj.ki.5002518. Epub 2007 Sep 5.

Reference Type RESULT
PMID: 17805238 (View on PubMed)

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. doi: 10.1038/sj.ki.5002466. Epub 2007 Aug 29.

Reference Type RESULT
PMID: 17728707 (View on PubMed)

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.

Reference Type DERIVED
PMID: 40576086 (View on PubMed)

Ruggeri M, Bellasi A, Cipriani F, Molony D, Bell C, Russo D, Di Iorio B. Sevelamer is cost effective versus calcium carbonate for the first-line treatment of hyperphosphatemia in new patients to hemodialysis: a patient-level economic evaluation of the INDEPENDENT-HD study. J Nephrol. 2015 Oct;28(5):593-602. doi: 10.1007/s40620-014-0122-8. Epub 2014 Jul 16.

Reference Type DERIVED
PMID: 25027030 (View on PubMed)

Di Iorio BR, Cucciniello E, Bellizzi V. Vascular calcification and QT interval in incident hemodialysis patients. J Nephrol. 2009 Nov-Dec;22(6):694-8.

Reference Type DERIVED
PMID: 19967647 (View on PubMed)

Other Identifiers

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2008.1.brd.renagel

Identifier Type: -

Identifier Source: secondary_id

2008.1

Identifier Type: -

Identifier Source: org_study_id

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