L-carnitine as an adjunct treatment for septic shock patients with acute kidney injury: a multicentre, randomized, 2-parallel group, superiority trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nimes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Trial duration

12 Jan 2018 → ongoing

Decision date (initial)

2024-04-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

DGOS/CHUNimes

External identifiers

EU CT number

2024-512508-21-00

EudraCT number

2016-001977-34

ClinicalTrials.gov

NCT02664753

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

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.

Secondary objectives 5

1. 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
2. B. To compare study arms in terms of patient safety.
3. C. To compare study arms in terms of further clinical outcomes, with special emphasis on nephrological outcomes.
4. 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.
5. 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).

Conditions and MedDRA coding

shock septic

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. • 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
2. • The patient must be insured or beneficiary of a health insurance plan
3. • The patient is at least 18 years old
4. • 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
5. 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)
6. • The patient has acute renal insufficiency with an KDIGO score of 3
7. • The patient has started continuous renal replacement therapy (CRRT) or intermittent renal replacement therapy (IRRT) within the past 72 hours, or will start RRT (CRRT or IRRT) within the next 72 hours.

Exclusion criteria 16

1. • 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
2. • The patient is in an exclusion period determined by a previous study
3. • The patient is under judicial protection, or is an adult under guardianship
4. • The patient is pregnant, parturient or breastfeeding
5. • 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)
6. • If the patient is unable to sign a consent form: the patient-designated trusted person or family member refuses to sign the consent form
7. • If the patient is unable to sign a consent form: It is impossible to correctly inform the patient-designated trusted person or family member
8. • The patient is able/apt to sign a consent form, but refuses to do so
9. • The patient is able/apt to sign a consent form, but cannot be correctly informed
10. • Septic shock without associated AKI
11. • Patients with a known allergy to L-Carnitine or other component of levocarnil oral solution or for injection
12. • Pre-existing chronic disease requiring dialysis
13. • The patient has stage 4 CKD with baseline DFG (CDK) if known <30 ml
14. • History of seizures or epilepsy
15. • Chronic bowel disease or history of chronic diarrhoea
16. • Under treatment with sodium valproate

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mortality

Secondary endpoints 9

1. Mortality
2. Survival (verification of vital status and collection of death certificates to determine date of death)
3. Days alive and not on renal replacement therapy
4. Days alive and free of renal failure
5. Days alive and free of organ failure
6. Days alive and not on mechanical ventilation
7. Days alive and not in ICU
8. Days alive and not in hospital
9. Days alive and free of catecholamines

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nimes

Sponsor organisation

Centre Hospitalier Universitaire De Nimes

Address

Place Du Professeur Robert Debre

City

Nimes Cedex 9

Postcode

30029

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nimes

Contact name

Simonet Anne Clarisse

Public contact point

Organisation

Centre Hospitalier Universitaire De Nimes

Contact name

Simonet Anne Clarisse

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications