Clinical trial NCT00710788: Reduce Cardiovascular Calcifications to Reduce QT Interval in Dialysis
Official title: Interventional, Multicenter, Prospective, Randomized Trial to Slow Down the Progression of Cardiovascular Calcifications to Reduce QTd in Incident Dialysis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Mortality
Keywords: QT interval
QT dispersion
arrhythmias
death
TC score
Lead sponsor: Azienda Sanitaria ASL Avellino 2
Sponsor class: OTHER
First posted: 2008-07-04
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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 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.

Primary outcomes:
measure: death due to cardiac arrhythmias or as sudden cardiac death defined as any deaths coded as "cardiac arrest, cause unknown" or "cardiac arrhythmia" without any exclusions
timeFrame: 2 years
Secondary outcomes:
measure: QT interval; PWV; mortality for acute myocardial infarction, cerebral vascular accident and heart failure; Non-CV mortality
timeFrame: 2 years
Other outcomes:
Locations:
city: Solofra
country: Italy
facility: Nephrology Division
state: Avellino
Study officials:
affiliation: ASL AV/2, Avellino, Italy
name: Biagio R Di Iorio, MD, PhD
role: STUDY_CHAIR
affiliation: Nephrology Division, Medical School, University of Foggia
name: Loreto Gesualdo, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: ASL FG, Italy
name: Filippo Aucella, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AO MOscati, Avellino, Italy
name: Walter De Simone, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dialysis, Torre del Greco, Italy
name: Mario Migliorati, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nephrology Division, Medical School, University of Messina, Italy
name: Domenico Santoro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nephrology Division, ASL AV1, Sant'Angelo de Lomnardi, Italy
name: Pasquale Guastaferro, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dialysis, Avellino, Italy
name: Luigi Chiuchuilo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dialysis, Montella, Italy
name: Vincenzo Tedesco, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.