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L-carnitine as an Adjunct Treatment for Septic Shock Patients With Acute Kidney Injury (CarniSave)

Primary Purpose

Severe Sepsis, Shock, Septic, Acute Kidney Injury

Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
56 days of weight-adjusted L-Carnitine treatment
10 days of intravenous placebo (isotonic saline)
Sponsored by
Centre Hospitalier Universitaire de Nīmes
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Sepsis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 past 24 hours, or will start RRT (CRRT or IRRT) within the next 24 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

Sites / Locations

  • CHU de CaenRecruiting
  • CH de ChartresRecruiting
  • CHU de Clermont FerrandRecruiting
  • CHU de DijonRecruiting
  • CHU Lyon
  • APHM - Hôpital Nord
  • APHM - Hôpital de la Conception
  • APHM - Hôpital de la Timone Adultes
  • CHU de Montpellier - St EloiRecruiting
  • CHU de Montpellier - LapeyronieRecruiting
  • CHU de Nîmes - Hôpital Universitaire CarémeauRecruiting
  • CHU de PoitiersRecruiting
  • CHU de St Etienne
  • CHU de Toulouse - Hôpital RangueilRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

L-Carnitine group

Placebo then open group

Arm Description

Patients in the experimental arm will receive 10 days of intravenous L-carnitine treatment followed by 46 days of oral L-Carnitine treatment. Intervention: 56 days of weight-adjusted L-Carnitine treatment

Patients in the placebo arm will receive 10 days of intravenous isotonic saline in a fashion analogous to the experimental arm (they study is thus blinded for the first 10 days and then open there afterwards). Intervention: 10 days of intravenous placebo (isotonic saline)

Outcomes

Primary Outcome Measures

Mortality

Secondary Outcome Measures

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.
Mortality
Adverse Events per patient
Survival
The number of days alive and not on renal replacement therapy
The number of days alive and free of renal failure
The number of days alive and free of organ failure
The number of days alive and not on mechanical ventilation
The number of days alive and not in Intensive Care Unit (ICU)
The number of days alive and not in hospital
The number of days alive and free of (not requiring) catecholamines
A vector of repeated measures of daily SOFA (Sequential Organ Failure Assessment score) scores available during the ICU stay
Available daily scores will be aggregated into a vector for repeated measures analysis (similar to the agregation required for calculating a slope).
A vector of repeated measures of AKIN (Acute Kidney Injury Network score) score available during the ICU stay
Available daily scores will be aggregated into a vector for repeated measures analysis (similar to the agregation required for calculating a slope).
A vector of repeated measures of serum creatinine
Available measures will be aggregated into a vector for repeated measures analysis (similar to the agregation required for calculating a slope).
A vector of repeated measures of serum creatinine
Available measures will be aggregated into a vector for repeated measures analysis (similar to the agregation required for calculating a slope).
A vector of repeated measures of lactate levels available during the ICU stay
Available measures will be aggregated into a vector for repeated measures analysis (similar to the agregation required for calculating a slope).
Glomerular filtration rate (EpiCKD)
(if the patient is on dialysis, the glomerular filtration rate is set at 0)
Glomerular filtration rate (EpiCKD)
(if the patient is on dialysis, the glomerular filtration rate is set at 0)
Glomerular filtration rate (EpiCKD)
(if the patient is on dialysis, the glomerular filtration rate is set at 0)
Glomerular filtration rate (EpiCKD)
(if the patient is on dialysis, the glomerular filtration rate is set at 0)
Glomerular filtration rate (EpiCKD)
(if the patient is on dialysis, the glomerular filtration rate is set at 0)
Glomerular filtration rate (EpiCKD)
(if the patient is on dialysis, the glomerular filtration rate is set at 0)
Serum free carnitine level
Serum free carnitine level
Serum free carnitine level
Serum free carnitine level
Serum free carnitine level
Serum free carnitine level
Serum total carnitine level
Serum total carnitine level
Serum total carnitine level
Serum total carnitine level
Serum total carnitine level
Serum total carnitine level

Full Information

First Posted
January 19, 2016
Last Updated
February 13, 2023
Sponsor
Centre Hospitalier Universitaire de Nīmes
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1. Study Identification

Unique Protocol Identification Number
NCT02664753
Brief Title
L-carnitine as an Adjunct Treatment for Septic Shock Patients With Acute Kidney Injury
Acronym
CarniSave
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

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 5, 2018 (Actual)
Primary Completion Date
April 2024 (Anticipated)
Study Completion Date
April 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Nīmes

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Sepsis, Shock, Septic, Acute Kidney Injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
272 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
L-Carnitine group
Arm Type
Experimental
Arm Description
Patients in the experimental arm will receive 10 days of intravenous L-carnitine treatment followed by 46 days of oral L-Carnitine treatment. Intervention: 56 days of weight-adjusted L-Carnitine treatment
Arm Title
Placebo then open group
Arm Type
Placebo Comparator
Arm Description
Patients in the placebo arm will receive 10 days of intravenous isotonic saline in a fashion analogous to the experimental arm (they study is thus blinded for the first 10 days and then open there afterwards). Intervention: 10 days of intravenous placebo (isotonic saline)
Intervention Type
Drug
Intervention Name(s)
56 days of weight-adjusted L-Carnitine treatment
Intervention Description
Patients in the experimental arm will receive 10 days of intravenous L-carnitine treatment followed by 46 days of oral L-Carnitine treatment. Day 1: a first bolus of 6g of L-Carnitine is administered with a syringe driver of 50 ml. Day 2 to Day 10: Two mini-perfusions are prepared each day, corresponding to 1 administration every 12 hours. 50 mg/kg/day (rounded up to the next gram) L-Carnitine is added to each syringes For the next 46 days, patients will take oral doses of L-Carnitine as follows: < à 60kg : 2g/day > 60kg : 3g/day If the patient leaves the hospital before D10, oral treatment can be initiated at the end of the hospitalization
Intervention Type
Drug
Intervention Name(s)
10 days of intravenous placebo (isotonic saline)
Intervention Description
Patients in the placebo arm will receive 10 days of intravenous isotonic saline in a fashion analogous to the experimental arm (they study is thus blinded for the first 10 days and then open there afterwards). Day 1: 1 50ml syringe driver of 50 ml isotonic saline solution . Day 2 to Day 10 : Two syringe drivers of 50 ml of isotonic saline solution are prepared each day, one during the morning and one during the evening.
Primary Outcome Measure Information:
Title
Mortality
Time Frame
28 days
Secondary Outcome Measure Information:
Title
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.
Description
Mortality
Time Frame
10 days
Title
Adverse Events per patient
Time Frame
12 months (throughout study)
Title
Survival
Time Frame
12 months (throughout study)
Title
The number of days alive and not on renal replacement therapy
Time Frame
12 months
Title
The number of days alive and free of renal failure
Time Frame
12 months
Title
The number of days alive and free of organ failure
Time Frame
12 months
Title
The number of days alive and not on mechanical ventilation
Time Frame
12 months
Title
The number of days alive and not in Intensive Care Unit (ICU)
Time Frame
12 months
Title
The number of days alive and not in hospital
Time Frame
12 months
Title
The number of days alive and free of (not requiring) catecholamines
Time Frame
12 months
Title
A vector of repeated measures of daily SOFA (Sequential Organ Failure Assessment score) scores available during the ICU stay
Description
Available daily scores will be aggregated into a vector for repeated measures analysis (similar to the agregation required for calculating a slope).
Time Frame
at ICU discharge (expected max of 28 days)
Title
A vector of repeated measures of AKIN (Acute Kidney Injury Network score) score available during the ICU stay
Description
Available daily scores will be aggregated into a vector for repeated measures analysis (similar to the agregation required for calculating a slope).
Time Frame
at ICU discharge (expected max of 28 days)
Title
A vector of repeated measures of serum creatinine
Description
Available measures will be aggregated into a vector for repeated measures analysis (similar to the agregation required for calculating a slope).
Time Frame
at ICU discharge (expected max of 28 days)
Title
A vector of repeated measures of serum creatinine
Description
Available measures will be aggregated into a vector for repeated measures analysis (similar to the agregation required for calculating a slope).
Time Frame
at discharge from the nephrology department (expected max of 60 days)
Title
A vector of repeated measures of lactate levels available during the ICU stay
Description
Available measures will be aggregated into a vector for repeated measures analysis (similar to the agregation required for calculating a slope).
Time Frame
at ICU discharge (expected max of 28 days)
Title
Glomerular filtration rate (EpiCKD)
Description
(if the patient is on dialysis, the glomerular filtration rate is set at 0)
Time Frame
month 1
Title
Glomerular filtration rate (EpiCKD)
Description
(if the patient is on dialysis, the glomerular filtration rate is set at 0)
Time Frame
month 2
Title
Glomerular filtration rate (EpiCKD)
Description
(if the patient is on dialysis, the glomerular filtration rate is set at 0)
Time Frame
month 3
Title
Glomerular filtration rate (EpiCKD)
Description
(if the patient is on dialysis, the glomerular filtration rate is set at 0)
Time Frame
month 6
Title
Glomerular filtration rate (EpiCKD)
Description
(if the patient is on dialysis, the glomerular filtration rate is set at 0)
Time Frame
month 9
Title
Glomerular filtration rate (EpiCKD)
Description
(if the patient is on dialysis, the glomerular filtration rate is set at 0)
Time Frame
month 12
Title
Serum free carnitine level
Time Frame
baseline
Title
Serum free carnitine level
Time Frame
after 48h of renal replacement therapy
Title
Serum free carnitine level
Time Frame
day 7
Title
Serum free carnitine level
Time Frame
day 14
Title
Serum free carnitine level
Time Frame
month 1
Title
Serum free carnitine level
Time Frame
month 2
Title
Serum total carnitine level
Time Frame
baseline
Title
Serum total carnitine level
Time Frame
after 48h of renal replacement therapy
Title
Serum total carnitine level
Time Frame
day 7
Title
Serum total carnitine level
Time Frame
day 14
Title
Serum total carnitine level
Time Frame
month 1
Title
Serum total carnitine level
Time Frame
month 2

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 past 24 hours, or will start RRT (CRRT or IRRT) within the next 24 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pascal Reboul, MD
Phone
+33.(0)4.66.68.35.56
Email
pascal.reboul@chu-nimes.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Carey Suehs, PhD
Phone
+33.(0)4.66.68.67.88
Email
carey.suehs@chu-nimes.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pascal Reboul, MD
Organizational Affiliation
Centre Hospitalier Universitaire de Nîmes
Official's Role
Study Director
Facility Information:
Facility Name
CHU de Caen
City
Caen Cedex 9
ZIP/Postal Code
14033
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thierry Lobbedez, MD, PhD
First Name & Middle Initial & Last Name & Degree
Damien Ducheyron, MD, PhD
Facility Name
CH de Chartres
City
Chartres
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre Kalfon
First Name & Middle Initial & Last Name & Degree
pierre kalfon
Facility Name
CHU de Clermont Ferrand
City
Clermont Ferrand
ZIP/Postal Code
63003
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bertrand Souweine, MD, PhD
First Name & Middle Initial & Last Name & Degree
Anne-Elizabeth Heng, MD
Facility Name
CHU de Dijon
City
Dijon
ZIP/Postal Code
21079
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean-Pierre Quenot, MD
First Name & Middle Initial & Last Name & Degree
Jean-Michel Rebibou, MD
Facility Name
CHU Lyon
City
Lyon
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
RIMMELE Thomas, MD
Facility Name
APHM - Hôpital Nord
City
Marseille Cedex 20
ZIP/Postal Code
13915
Country
France
Individual Site Status
Withdrawn
Facility Name
APHM - Hôpital de la Conception
City
Marseille
ZIP/Postal Code
13385
Country
France
Individual Site Status
Withdrawn
Facility Name
APHM - Hôpital de la Timone Adultes
City
Marseille
ZIP/Postal Code
13385
Country
France
Individual Site Status
Withdrawn
Facility Name
CHU de Montpellier - St Eloi
City
Montpellier cedex 5
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Samir Jaber, MD, PhD
Facility Name
CHU de Montpellier - Lapeyronie
City
Montpellier
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kada Klouche, MD, PhD
First Name & Middle Initial & Last Name & Degree
Olivier Jonquet, MD, PhD
First Name & Middle Initial & Last Name & Degree
Georges Mourad, MD, PhD
Facility Name
CHU de Nîmes - Hôpital Universitaire Carémeau
City
Nîmes Cedex 09
ZIP/Postal Code
30029
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laurent Muller, MD, PhD
First Name & Middle Initial & Last Name & Degree
Saber Barbar, MD
First Name & Middle Initial & Last Name & Degree
Jean-Yves Lefrant, MD, PhD
First Name & Middle Initial & Last Name & Degree
Olivier Moranne, MD, PhD
First Name & Middle Initial & Last Name & Degree
Serge Lumbroso, MD, PhD
First Name & Middle Initial & Last Name & Degree
David-Paul de Brauwère, MD
Facility Name
CHU de Poitiers
City
Poitiers Cedex
ZIP/Postal Code
86021
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
claire DAHYOT-FIZELIER, MD, PhD
First Name & Middle Initial & Last Name & Degree
Frank Bridoux, MD, PhD
First Name & Middle Initial & Last Name & Degree
thibaut papet
First Name & Middle Initial & Last Name & Degree
marc bauwens
Facility Name
CHU de St Etienne
City
Saint-Priest en Jarez
ZIP/Postal Code
42270
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric Alamartine, MD, PhD
First Name & Middle Initial & Last Name & Degree
Christophe Mariat, MD, PhD
Facility Name
CHU de Toulouse - Hôpital Rangueil
City
Toulouse Cedex 9
ZIP/Postal Code
31059 T
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dominique Chauveau, MD, PhD
First Name & Middle Initial & Last Name & Degree
Olivier Cointault, MD
First Name & Middle Initial & Last Name & Degree
nassim kamar
First Name & Middle Initial & Last Name & Degree
stanislas faguer

12. IPD Sharing Statement

Citations:
PubMed Identifier
12682500
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.
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L-carnitine as an Adjunct Treatment for Septic Shock Patients With Acute Kidney Injury

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