Reduce Cardiovascular Calcifications to Reduce QT Interval in Dialysis

Cardiovascular Mortality Clinical Trial

— Independent  

Official title:

Interventional, Multicenter, Prospective, Randomized Trial to Slow Down the Progression of Cardiovascular Calcifications to Reduce QTd in Incident Dialysis Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00710788
• Other study ID #: 2008.1
• Secondary ID: 2008.1.brd.renag
• Status: Completed
• Phase: N/A
• First received: July 2, 2008
• Last updated: February 9, 2013
• Start date: January 2007
• Est. completion date: September 2011

Study information

• Verified date: February 2013
• Source: Azienda Sanitaria ASL Avellino 2
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 360
• Est. completion date: September 2011
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Calcinosis
• Cardiovascular Mortality

Intervention

Drug:
• sevelamer phosphate-binders
1600 mg/day for 2 years
• Calcium Carbonate
Calcium carbonate 1 g/day for 2 years

Locations

Country	Name	City	State
Italy	Nephrology Division	Solofra	Avellino

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Sanitaria ASL Avellino 2

Country where clinical trial is conducted

Italy, 

References & Publications (16)

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. doi: 10.1159/000130696. Review. — View 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

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. — View 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. Epub 2006 Jul 31. — View Citation

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 — View 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. — View 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. — View 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. Review. — View 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. Review. Spanish. — View 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. — View 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. Epub 2007 S — View 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 us — View 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. Epub — View 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. — View 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. — View 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. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		2 years	Yes
Secondary	QT interval; PWV; mortality for acute myocardial infarction, cerebral vascular accident and heart failure; Non-CV mortality		2 years	Yes