Clinical trial NCT02664753: L-carnitine as an Adjunct Treatment for Septic Shock Patients With Acute Kidney Injury
Official title: L-carnitine as an Adjunct Treatment for Septic Shock Patients With Acute Kidney Injury: a Multicentre, Randomized, 2-parallel Group, Superiority Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Severe Sepsis
Shock, Septic
Acute Kidney Injury
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2016-01-27
Enrollment: 272
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to compare 28 day mortality rates between septic shock patients with acute renal insufficiency treated via L-Carnitine (as an adjunct therapy) versus a similar group of patients not receiving L-Carnitine adjunct therapy.

Detailed description: The secondary objectives of this study are:

A. First secondary objective of this study is to compare 10 day mortality rates of septic shock patients with renal insufficiency treated via L-Carnitine (as an adjunct therapy) for 56 days versus a patients not receiving L-Carnitine adjunct therapy

B. To compare study arms in terms of patient safety.

C. To compare study arms in terms of further clinical outcomes, with special emphasis on nephrological outcomes.

D. To study (and compare between arms) the kinetic curves of free and total serum carnitine. Renal replacement therapy rapidly depletes the body's carnitine levels. Tracking adequate carnitine levels is therefore important for the interpretation of study results.

E. To constitute a bio-bank in association with the study for future ancillary studies (e.g. kidney injury marker studies, carnitine-responders versus non-responders, and other exploratory studies.

Eligibility criteria: Inclusion Criteria:

* • The emergency inclusion procedure was correctly applied according to French law (signature of consent form by a patient-designated trusted person or a family member, or a medical decision to proceed with patient inclusion if the latter two persons are unavailable) ---- OR ---- signature of the consent form by the patient

  * The patient must be insured or beneficiary of a health insurance plan
  * The patient is at least 18 years old
  * The patient was admitted to an intensive care unit (participating in the study) for sepsis or septic shock and presented with acute renal failure requiring, at some point, the use of extra-renal purification.
  * • The patient has sepsis or septic shock according to international criteria SEPSIS 3 (Singer et al, The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) ; JAMA. 2016)
  * The patient has acute renal insufficiency with an KDIGO score of 3
  * The patient has started continuous renal replacement therapy (CRRT) or intermittent renal replacement therapy (IRRT) within the previous 72 hours, or will start RRT (CRRT or IRRT) within the next 72 hours.

Exclusion Criteria:

* • The patient is participating in, or has participated in over the past three months, another interventional study that may interfere with the results or conclusions of this study

  * The patient is in an exclusion period determined by a previous study
  * The patient is under judicial protection, or is an adult under guardianship
  * The patient is pregnant, parturient or breastfeeding
  * The patient is susceptible to procreate and does not use methods of effective contraception (contraceptive hormonal ring, surgical contraception, contraceptive implant, contraceptive pill, male or female sheaths, skin patch, intrauterine contraceptive device)
  * If the patient is unable to sign a consent form: the patient-designated trusted person or family member refuses to sign the consent form
  * If the patient is unable to sign a consent form: It is impossible to correctly inform the patient-designated trusted person or family member
  * The patient is able/apt to sign a consent form, but refuses to do so
  * The patient is able/apt to sign a consent form, but cannot be correctly informed
  * Septic shock without associated AKI
  * Patients with a known allergy to L-Carnitine or other component of levocarnil oral solution or for injection
  * Pre-existing chronic disease requiring dialysis
  * The patient has stage 4 CKD with baseline DFG (CDK) if known \<30 ml
  * History of seizures or epilepsy
  * Chronic bowel disease or history of chronic diarrhoea
  * Under treatment with sodium valproate

Primary outcomes:
measure: Mortality
timeFrame: 28 days
Secondary outcomes:
measure: First secondary objective of this study is to compare 10 day mortality rates of septic shock patients with renal insufficiency treated via L-Carnitine (as an adjunct therapy) for 56 days versus a patients not receiving L-Carnitine adjunct therapy.
timeFrame: 10 days
measure: Adverse Events per patient
timeFrame: 12 months (throughout study)
measure: Survival
timeFrame: 12 months (throughout study)
measure: The number of days alive and not on renal replacement therapy
timeFrame: 12 months
measure: The number of days alive and free of renal failure
timeFrame: 12 months
measure: The number of days alive and free of organ failure
timeFrame: 12 months
measure: The number of days alive and not on mechanical ventilation
timeFrame: 12 months
measure: The number of days alive and not in Intensive Care Unit (ICU)
timeFrame: 12 months
measure: The number of days alive and not in hospital
timeFrame: 12 months
measure: The number of days alive and free of (not requiring) catecholamines
timeFrame: 12 months
measure: A vector of repeated measures of daily SOFA (Sequential Organ Failure Assessment score) scores available during the ICU stay
timeFrame: at ICU discharge (expected max of 28 days)
measure: A vector of repeated measures of AKIN (Acute Kidney Injury Network score) score available during the ICU stay
timeFrame: at ICU discharge (expected max of 28 days)
measure: A vector of repeated measures of serum creatinine
timeFrame: at ICU discharge (expected max of 28 days)
measure: A vector of repeated measures of serum creatinine
timeFrame: at discharge from the nephrology department (expected max of 60 days)
measure: A vector of repeated measures of lactate levels available during the ICU stay
timeFrame: at ICU discharge (expected max of 28 days)
measure: Glomerular filtration rate (EpiCKD)
timeFrame: month 1
measure: Glomerular filtration rate (EpiCKD)
timeFrame: month 2
measure: Glomerular filtration rate (EpiCKD)
timeFrame: month 3
measure: Glomerular filtration rate (EpiCKD)
timeFrame: month 6
measure: Glomerular filtration rate (EpiCKD)
timeFrame: month 9
measure: Glomerular filtration rate (EpiCKD)
timeFrame: month 12
measure: Serum free carnitine level
timeFrame: baseline
measure: Serum free carnitine level
timeFrame: after 48h of renal replacement therapy
measure: Serum free carnitine level
timeFrame: day 7
measure: Serum free carnitine level
timeFrame: day 14
measure: Serum free carnitine level
timeFrame: month 1
measure: Serum free carnitine level
timeFrame: month 2
measure: Serum total carnitine level
timeFrame: baseline
measure: Serum total carnitine level
timeFrame: after 48h of renal replacement therapy
measure: Serum total carnitine level
timeFrame: day 7
measure: Serum total carnitine level
timeFrame: day 14
measure: Serum total carnitine level
timeFrame: month 1
measure: Serum total carnitine level
timeFrame: month 2
Other outcomes:
Locations:
city: Caen Cedex 9
country: France
facility: CHU de Caen
city: Chartres
country: France
facility: CH de Chartres
city: Clermont Ferrand
country: France
facility: CHU de Clermont Ferrand
city: Dijon
country: France
facility: CHU de Dijon
city: Lyon
country: France
facility: CHU Lyon
city: Marseille Cedex 20
country: France
facility: APHM - Hôpital Nord
city: Marseille
country: France
facility: APHM - Hôpital de la Conception
city: Marseille
country: France
facility: APHM - Hôpital de la Timone Adultes
city: Montpellier cedex 5
country: France
facility: CHU de Montpellier - St Eloi
city: Montpellier
country: France
facility: CHU de Montpellier - Lapeyronie
city: Nîmes Cedex 09
country: France
facility: CHU de Nîmes - Hôpital Universitaire Carémeau
city: Poitiers Cedex
country: France
facility: CHU de Poitiers
city: Saint-Priest en Jarez
country: France
facility: CHU de St Etienne
city: Toulouse Cedex 9
country: France
facility: CHU de Toulouse - Hôpital Rangueil
Study officials:
affiliation: Centre Hospitalier Universitaire de Nîmes
name: Pascal Reboul, MD
role: STUDY_DIRECTOR
References:
citation: Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G; SCCM/ESICM/ACCP/ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6. doi: 10.1097/01.CCM.0000050454.01978.3B.