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Exposure to serious adverse events related to the research (i.e., death), the mnts = 54% versus 58 deaths out of 121 patients = 48%).onitoring committee unanimously recommended discontinuation of the trial.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| L-Carnitine group | Experimental | 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 |
|
| Placebo then open group | Placebo Comparator | 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) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 56 days of weight-adjusted L-Carnitine treatment | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Mortality | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 10 days |
| Adverse Events per patient |
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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
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
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| Name | Affiliation | Role |
|---|---|---|
| Pascal Reboul, MD | Centre Hospitalier Universitaire de Nīmes | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU de Caen | Caen | 14033 | France | |||
| CH de Chartres |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12682500 | Background | 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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|
| 10 days of intravenous placebo (isotonic saline) | Drug | 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. |
|
| 12 months (throughout study) |
| Survival | 12 months (throughout study) |
| The number of days alive and not on renal replacement therapy | 12 months |
| The number of days alive and free of renal failure | 12 months |
| The number of days alive and free of organ failure | 12 months |
| The number of days alive and not on mechanical ventilation | 12 months |
| The number of days alive and not in Intensive Care Unit (ICU) | 12 months |
| The number of days alive and not in hospital | 12 months |
| The number of days alive and free of (not requiring) catecholamines | 12 months |
| 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). | at ICU discharge (expected max of 28 days) |
| 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). | at ICU discharge (expected max of 28 days) |
| 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). | at ICU discharge (expected max of 28 days) |
| 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). | at discharge from the nephrology department (expected max of 60 days) |
| 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). | at ICU discharge (expected max of 28 days) |
| Glomerular filtration rate (EpiCKD) | (if the patient is on dialysis, the glomerular filtration rate is set at 0) | month 1 |
| Glomerular filtration rate (EpiCKD) | (if the patient is on dialysis, the glomerular filtration rate is set at 0) | month 2 |
| Glomerular filtration rate (EpiCKD) | (if the patient is on dialysis, the glomerular filtration rate is set at 0) | month 3 |
| Glomerular filtration rate (EpiCKD) | (if the patient is on dialysis, the glomerular filtration rate is set at 0) | month 6 |
| Glomerular filtration rate (EpiCKD) | (if the patient is on dialysis, the glomerular filtration rate is set at 0) | month 9 |
| Glomerular filtration rate (EpiCKD) | (if the patient is on dialysis, the glomerular filtration rate is set at 0) | month 12 |
| Serum free carnitine level | baseline |
| Serum free carnitine level | after 48h of renal replacement therapy |
| Serum free carnitine level | day 7 |
| Serum free carnitine level | day 14 |
| Serum free carnitine level | month 1 |
| Serum free carnitine level | month 2 |
| Serum total carnitine level | baseline |
| Serum total carnitine level | after 48h of renal replacement therapy |
| Serum total carnitine level | day 7 |
| Serum total carnitine level | day 14 |
| Serum total carnitine level | month 1 |
| Serum total carnitine level | month 2 |
| Chartres |
| France |
| CHU de Clermont Ferrand | Clermont-Ferrand | 63003 | France |
| CHU de Dijon | Dijon | 21079 | France |
| CHU Lyon | Lyon | France |
| CHU de Montpellier - Lapeyronie | Montpellier | 34295 | France |
| CHU de Montpellier - St Eloi | Montpellier | 34295 | France |
| CHU de Nîmes - Hôpital Universitaire Carémeau | Nîmes | 30029 | France |
| CHU de Poitiers | Poitiers | 86021 | France |
| CHU de St Etienne | Saint-Priest-en-Jarez | 42270 | France |
| CHU de Toulouse - Hôpital Rangueil | Toulouse | 31059 T | France |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D012772 | Shock, Septic |
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
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