Septic Shock
Conditions
Brief summary
Sepsis-associated encephalopathy is associated with high mortality rates and long-term neuropsychiatric disorders. Currently, there is no specific treatment for sepsis-associated encephalopathy. Levetiracetam, a broad-spectrum antiepileptic widely used in intensive care units, has neuroprotective properties. We propose the KiSS study, a multicenter, prospective, randomized, double-blind trial with two arms, evaluating the effect of levetiracetam treatment for seven days during septic shock on the occurrence and duration of sepsis-associated encephalopathy.
Interventions
DRUGLevetiracetam IV
1000 mg twice a day during 7 days maximum
OTHERPlacebo control
NaCl 0.9% sodium chloride in the same route and method of administration as experimental treatment
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double blind
Intervention model description
Phase III, multicenter, comparative, randomized, double-blind, placebo-controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Aged 18 years or older * Hospitalized in intensive care for less than 96 hours * Presenting with septic shock evolving for less than 24 hours defined by: 1. Clinically or microbiologically documented infection and 2. SOFA score ≥ 2 or an increase in SOFA score ≥ 2 points if organ dysfunction was present before the infection and 3. Need for vasopressor administration to maintain a mean arterial pressure ≥ 65mmHg and 4. Lactate level \> 2mmol/L (18mg/dL) despite adequate fluid resuscitation * Patient's consent, their next of kin consent, or emergency inclusion Non inclusion criteria : * Chronic long-term antiepileptic treatment upon admission or patient with uncontrolled seizures * Chronic or progressive central neurological pathologies of traumatic, inflammatory, vascular, infectious, neoplastic, or degenerative origin, defined by cognitive impairments preventing independent living or an IQCODE score \> 4.5 * Patient with moderate to severe dementia * Patient with psychiatric history and/or suicide attempts * Severe head trauma within the past 3 months * Patients with limitations on active therapies or for whom therapeutic commitment is not maximal * Patient presenting a prolonged QTc interval on ECG and/or at risk of cardiovascular disease * Concomitant treatment with Methotrexate during the administration of the investigational treatment * Allergy to levetiracetam * Minor patients * Ongoing pregnancy (blood or urinary βHCG) * Breastfeeding women * Patients under guardianship or trusteeship * Non-affiliation with social security or CMU * Participation in another interventional trial with a drug that may interact with levetiracetam or may impact the evaluation of KiSS trial outcomes. In case of doubt, please contact the trial's coordinating investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of days alive without delirium or coma | 14 days after randomization |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality in hospital | At day 28 | — |
| Overall survival | At day 90 | — |
| Duration of mechanical ventilation | At day 28 | — |
| Length of stay in intensive care unit | Up to day 90 | — |
| Length of stay in hospital | Up to day 90 | — |
| Occurrence of epileptic seizures | Up to day 14 | From Day 1 to Day 14 (confirmed by EEG or tonic-clonic seizures) and/or occurrence of epileptic abnormalities (periodic epileptic discharges) |
| Mortality in intensive care | At day 28 | — |
| Severity of cognitive impairment | At day 90 | Evaluated by a telephone survey using Telephone MoCA (Montreal Cognitive Assessment). The scores ranges from 0 to 30. A score of 26 or higher is typically considered normal. A score of 25 or lower may indicate cognitive impairment, such as mild cognitive impairment (MCI) or early-stage dementia. |
| Severity of anxiety and depression | At day 90 | Assessed with HADS (Hospital Anxiety and Depression Scale) scale Score varies from 0 to 21 for each componant (Anxiety and depression) The higher the score, the more severe the anxiety or depression. |
| Presence of post-traumatic stress (PTSD) | At day 90 | Assessed by IES-R (Impact of Event Scale Revisited) The total score can range from 0 to 88. Higher scores indicate greater trauma-related distress and a higher likelihood of experiencing PTSD symptoms. |
| Quality of life scoring | At day 90 | Using EQ-5D-5L. It evaluates five dimensions : mobility, self-care, usual activities, pain/discomfort and anxiety/depression and each dimension has five levels : no problems, slight problems, moderate problems, severe problems and extreme problems. Answers are given on a 5-point scale by domain, the higher the score, the poorer the quality of life. |
| Autonomy in daily life | At day 90 | Using Katz Index of Independence in Activities of Daily Living (ADL) The score varies from 0 to 6, the lower the score, the more dependent the person. |
| Time between cessation of sedation and awakening | At day 90 | Defined by spontaneous eye opening, among patients not deceased under sedation |
Contacts
Primary ContactShidasp Siami, MD
Backup ContactJérôme Lambert, MD PhD
Outcome results
None listed