Nicotinamide Versus Sevelamer Hydrochloride on Phosphatemia Control on Chronic Hemodialysed Patients (NICOREN)

This study has been terminated.
(Financial problem)
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire, Amiens
ClinicalTrials.gov Identifier:
NCT01011699
First received: November 10, 2009
Last updated: May 13, 2016
Last verified: May 2016
  Purpose
The comparison between nicotinamide and sevelamer aims to demonstrate, in chronic hemodialysed patients, the non-inferiority of nicotinamide in terms of control of the phosphatemia. Secondary objectives is to compare the two treatments in terms of efficiency in other biological parameters, vascular calcification and bone mass loss and on the clinical and biological tolerance and finally to explore the roles of metabolites of nicotinamide.

Condition Intervention Phase
Chronic Renal Failure
Hemodialysis
Drug: nicotinamide
Drug: sevelamer
Drug: cinacalcet
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Comparison of Nicotinamide and Sevelamer Hydrochloride on Phosphatemia Control on Chronic Hemodialysed Patients

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire, Amiens:

Primary Outcome Measures:
  • The comparison between nicotinamide and Sevelamer was primarily to demonstrate the noninferiority of nicotinamide in terms of control of the phosphatemia observed during the 4th, 5th and 6th months before to introduce Cinacalcet ®. [ Time Frame: 6th months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To demonstrate noninferiority of nicotinamide in terms of effect on dyslipidemia (evaluated by the ratio LDL / HDL cholesterol), the risk of hypercalcemia (PCa> 2.37 mmol / l) and increase of phospho-calcic product (> 3 , 79 mmol/l). [ Time Frame: 6 th months and one year ] [ Designated as safety issue: Yes ]
  • To evaluate the difference between nicotinamide and sevelamer on vascular calcification [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • To evaluate the difference between nicotinamide and sevelamer on bone mass loss and fracture risk [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Evaluate the percentage of population requiring use of cinacalcet® to control PTH (75-300 pg/ml). Evaluate his benefit on phosphatemia and calcemia control. Prevent the need for surgical PTX, and evaluate the additional cost of treatment by cinacalcet [ Time Frame: 6th months ] [ Designated as safety issue: Yes ]
  • Evaluate roles of metabolites of nicotinamide (efficacy and side effects) through another study [ Time Frame: 6th months and one year ] [ Designated as safety issue: Yes ]
  • Compare the cost-effectiveness ratio of these two treatments [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Enrollment: 176
Study Start Date: January 2010
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: sevelamer

Titration phase with sevelamer (Renagel) with the aim of phosphatemia control in 4 weeks of treatment, with stable dose of calcic carbonate.

Increase of sevelamer dose up to 12 tablets, as follows:

0 morning, 2 noon, 2 evening (first week), then, 0 morning, 4 noon, 4 evening (second week), then, 2 morning, 4 noon, 4 evening (third week), then, 4 morning, 4 noon, 4 evening (fourth week).

Drug: sevelamer

Titration phase with sevelamer (Renagel) with the aim of phosphatemia control before 4 weeks of treatment, with stable dose of calcic carbonate.

Increase of sevelamer dose up to 12 tablets, as follows:

0 morning, 2 noon, 2 evening (first week), then, 0 morning, 4 noon, 4 evening (second week), then, 2 morning, 4 noon, 4 evening (third week), then, 4 morning, 4 noon, 4 evening (fourth week).

Other Names:
  • Renagel
  • ATC class V03AE02
Drug: cinacalcet

After 6 months of treatment, patient screening on PTH level:

For patients with PTH > 300pg/ml, introduction of cinacalcet by level of 30 mg every 3 weeks, up to 180mg daily (administered during the meal and before next dialysis) Cinacalcet increase will be stopped once PTH < 250 pg/ml. Calcic carbonate dose will be increase once calcemia will be < 2.25 mmol/l. If maximum tolerated dose is not sufficient to prevent hypocalcemia < 2.10 mmol/l calcium of dialysis bath wille be increased up to 1.75 mmol/l and calcic carbonate will be decreased.

A dose adjustment is possible with nicotinamide to obtain a phosphatemia between 1.10 and 1.60 mmol/l.

Other Names:
  • Mimpara
  • ATC class H05BX01
Active Comparator: nicotinamide

Titration phase with nicotinamide (Nicobion) with the aim of phosphatemia control in 4 weeks of treatment, with stable dose of calcic carbonate.

Increase of nicotinamide dose up to 4 tablets, as follows:

0 morning, 1 noon, 0 evening (first week), then, 0 morning, 1 noon, 1 evening (second week), then, 1 morning, 1 noon, 1 evening (third week), then, 1 morning, 2 noon, 1 evening (fourth week).

Drug: nicotinamide

Titration phase of nicotinamide (Nicobion) with the aim of phosphatemia control in 4 weeks with stable dose of calcic carbonate;

Increase of nicotinamide dose of Nicobion 500mg (nicotinamide 500mg), up to 4 tablets daily, as follows:

0 morning, 1 noon, 0 evening (first week), then, 0 morning, 1 noon, 1 evening (second week), then, 1 morning, 1 noon, 1 evening (third week), then, 1 morning, 2 noon, 1 evening (fourth week).

Other Names:
  • Nicobion
  • ATC class A11HA01
Drug: cinacalcet

After 6 months of treatment, patient screening on PTH level:

For patients with PTH > 300pg/ml, introduction of cinacalcet by level of 30 mg every 3 weeks, up to 180mg daily (administered during the meal and before next dialysis) Cinacalcet increase will be stopped once PTH < 250 pg/ml. Calcic carbonate dose will be increase once calcemia will be < 2.25 mmol/l. If maximum tolerated dose is not sufficient to prevent hypocalcemia < 2.10 mmol/l calcium of dialysis bath wille be increased up to 1.75 mmol/l and calcic carbonate will be decreased.

A dose adjustment is possible with nicotinamide to obtain a phosphatemia between 1.10 and 1.60 mmol/l.

Other Names:
  • Mimpara
  • ATC class H05BX01

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women or men over 18 years
  • Chronic hemodialysis (since more than 3 months)
  • Hyperphosphatemia controlled with only CaCO3
  • PO4 > 1,60 mmol/l, PCa < 2,37 mmol/l
  • patient able to understand and sign informed consent form

Exclusion Criteria:

  • PTH < 60 ou > 800 pg/ml (PTX)
  • Aluminium intoxication (aluminium level in blood > 0,5 µmol/l)
  • Score of aortic calcifications ≥ 20 (max 24)
  • Characterized intolerance with Renagel and/or Nicobion
  • Pregnant woman
  • Autoimmune disease
  • Patient known to have a bad drug compliance
  • Blood tests abnormality (thrombopenia <150 000, serum albumin <30g)
  • Hepatic tests abnormality
  • Transplant probably within 6 months
  • Patient who will need transplantation within 6 month
  • Patients receiving chemotherapy
  • Patients having a loss of dry weight of 3 kg in 3 months or 6 kg in 6 months.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01011699

Locations
France
Centre Hospitalier Général
Soissons, Aisne, France, 02009
Centre Hospitalier
Lisieux, Calvados, France, 14100
ALURAD
Limoges, Limousin, France, 87042
Association Régionale Promotion Dialyse à domicile (ARPDD)
Reims, Marne, France
Centre Hospitalier Universitaire
Reims, Marne, France, 51092
Association pour le Développement de l'Hémodialyse
Hénin-Beaumont, Nord-Pas de Calais, France, 62110
Polyclinique de la Louvière
Lille, Nord, France, 59000
CHRU
Lille, Nord, France, 59037
Hôpital Victor Provo
Roubaix, Nord, France, 59056
Centre Hospitalier Général
Valenciennes, Nord, France, 59322
Centre Hospitalier Général
Beauvais, Oise, France, 60000
Clinique Saint Côme
Compiegne, Oise, France, 60200
Centre Hospitalier Général
Creil, Oise, France, 60100
Clinique du Bois Bernard
Bois Bernard, Pas de calais, France, 62320
Centre Hospitalier
Boulogne sur mer, Pas de calais, France, 62200
Centre Hospital-Universitaire d'Amiens
Amiens, Picardie, France, 80054
Clinique de l'Europe
Rouen, Seine maritime, France, 76040
Centre Hospitalier
Cambrai, France, 59407
Sponsors and Collaborators
Centre Hospitalier Universitaire, Amiens
Investigators
Study Director: Albert FOURNIER, Pr Centre Hospitalier Universitaire, Amiens
Principal Investigator: Ziad MASSY, Pr Centre Hospitalier Universitaire, Amiens
  More Information

Publications:
Malluche M, Monier-faugère M, wang G, Frazao J, Coburn J, Baker N, McCary LC, Turner JA, Goodman WG: Cinaclacet Hcl reduces bone turn over and bone marrow fibrosa in hemodialysis patients with secondary hyperparathyroidism. ERA XLI congress. AbstractBook Lisboa:P218 (M016), 2004
Dament J,Gill M, Confer S, Jones C, Webster J: The bone kinetics of lanthanum in dialysis patient treated with lanthanum carbonate up to 45 years. J Am Soc Nephrol 15 (Abstract):271A (poster FPO 948), 2004
Malluche M, Faugère MC, Damment SJP, Webster I: No osteomalacia in dialysis patients treated with lanthanum carbonate up to 4.5 years. J Am Soc Nephrol 15 (supplt Abstract):p270A Poster F P0944,2004
De Smet R, Thermote F, Lameire N, Vanholder R: SEVELAMER hydrochloride (Renagel(r)) adsorbs the uremic compounds indoxyl sulfate, indole and p-creso.[Abstract]. J Am Soc Nephrol 15, 2004
Alsheikh-Ali A, Aboujaily HM, Stanek LJ, coll. e: Increases in HDL cholesterol are the strongest predictions of risk reduction in lipid intervention trials. Circulation 111 (suppltIII):813 Abstract 3754,2004

Responsible Party: Centre Hospitalier Universitaire, Amiens
ClinicalTrials.gov Identifier: NCT01011699     History of Changes
Other Study ID Numbers: PHRCIR08-PR-FOURNIER  Eudract N°2008-004673-17 
Study First Received: November 10, 2009
Last Updated: May 13, 2016
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Hospitalier Universitaire, Amiens:
nicotinamide
sevelamer hydrochloride
phosphatemia
cinacalcet
dyslipidemia
vascular calcification
bone mass loss

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Failure, Chronic
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Sevelamer
Cinacalcet Hydrochloride
Niacinamide
Niacin
Nicotinic Acids
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Calcimimetic Agents
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on July 25, 2016