Clinical trial NCT00322322: Early Administration of L-carnitine in Hemodialysis Patients
Official title: Early Administration of L-carnitine in Hemodialysis Patients: Double Blind Randomized Trial Versus Placebo
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Complication of Hemodialysis
Hyperthyroidism Treated or Under Control
Keywords: L-carnitine supplementation
Hemodialysis
Anaemia
Erythropoietin responsiveness
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2006-05-05
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: Hemodialysis is a cause of carnitine deficiency. The deficiency of carnitine induces an anemia by an increase fragility of the red blood cells, a muscular fatigue and a cardiac dysfunction. We proposed to evaluate the benefit of an early administration of L-carnitine in hemodialysis patients. The patients should be included in the first month after the start of chronic hemodialysis, randomized to receive L-carnitine or placebo and should be followed-up during one year.

Detailed description: The first aim of the study is to compare the resistance index to erythropoietin (hemoglobin level / rHuerythropoietin dose) with L-carnitine versus placebo Double blind randomized study evaluating the supplementation with L-carnitine versus placebo in patients beginning chronic hemodialysis for less than 1 month.

Primary outcome to compare rHuerythropoietin resistance index defined as hemoglobin level / rHuEPO dose ratio with L-carnitine and with placebo.

Secondary endpoints to compare acylcarnitine / carnitine ratio, number of red blood cells transfusion, physical status, quality of life, hypotensive episodes, lipid profile, diabetes profile, albuminemia, c reactive protein.

Several variables that influenced primary and secondary endpoints will be included in a multivariate analysis; albuminemia, c reactive protein, iron status, dialysis efficiency, protein intake, lipid intake, treatment with additional vitamins (C, B9, B6), treatment with statins, treatment of predialysis hypotension by midodrine, antihypertensive treatments.

Statistical analysis:

* description of the cohort
* comparisons of each evaluated variables between the 2 treatments
* ANOVA study for repeated measurements from inclusion to month-12 for Hb / rHuEPO dose to compare the course of the ratio between each group in intention to treat analysis
* analysis of the ratio Hb / rHuEPO month by month and taking into account tempera withdrawal

Following analysis in both intention to treat and per protocol analysis:

* acylcarnitine / carnitine ratio by ANOVA for repeated data
* number of predialysis hypotension by Chi2 test
* number of red blood cells transfusion by Chi2 test
* SF-36 physical status by comparison of mean
* SF-36 total score by comparison of mean
* lipid profile by ANOVA for repeated data
* HbA1c by ANOVA for repeated data
* variables that influenced primary and secondary variables will be analyzed by multivariate analysis
* statistical study of clinical events per month

Eligibility criteria: Inclusion Criteria:

* Patient with less than 1 month on hemodialysis.
* Treated with rHuEPO.
* Male or female aged of more than 18 years old.
* With contraception treatment for women of procreation age.
* Having received and understand information.

Exclusion Criteria:

* Patients with no need of rHuEPO
* Patients with cancer disease
* Patients with life expectancy under 6 months
* Patients having a proved carnitine deficiency before the start of hemodialysis

Primary outcomes:
measure: Resistance index to erythropoietin
timeFrame: during de study
measure: Haemoglobin level/weekly rHuerythropoietin dose in patients receiving l-carnitine versus those receiving the placebo.
timeFrame: during the study
Secondary outcomes:
measure: Acylcarnitine/carnitine ratio measured quarterly
timeFrame: during the study
measure: Number of red blood cells transfusion per patient during the study, data collected monthly
timeFrame: during the study
measure: Predialysis hypotension per patient during the study, data collected monthly
timeFrame: during the study
measure: SF 36 physical and total score at inclusion and at the end of the study
timeFrame: during the study
measure: Lipid profile, measured quarterly
timeFrame: during the study
measure: HbA1c, measured quarterly for diabetic patients and patients with glucose intolerance
timeFrame: during the study
measure: Albuminemia measured quarterly
timeFrame: during the study
measure: c reactive protein measured quarterly
timeFrame: during the study
Other outcomes:
Locations:
city: Paris
country: France
facility: Assistance Publique Hopitaux de Paris
city: Paris
country: France
facility: HOPITAL LA PITIE SALPETRIERE, service de Néphrologie
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Lucile Mercadal, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mercadal L, Tezenas du Montcel S, Chonchol MB, Debure A, Depreneuf H, Servais A, Bassilios N, Assogba U, Allouache M, Prie D. Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial. Am J Nephrol. 2018;48(5):349-356. doi: 10.1159/000494338. Epub 2018 Nov 8.