KISS Evaluation of early administration of Levetiracetam in the prevention and treatment of delirium during septic shock: a randomized, double-blind, placebo-controlled trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

31 Jul 2025 → ongoing

Decision date (initial)

2024-11-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

[DGOS - Ministry of Higher Education and Research] : PHRC Inter-régional 2019

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess the impact of early 7-day administration of levetiracetam in patients with septic shock hospitalized in the ICU on the number of days alive without coma or delirium at D14.

Secondary objectives 11

1. To evaluate the impact of treatment with levetiracetam versus placebo on mortality in intensive care, in hospital, at D28 and D90
2. To evaluate the impact of treatment with levetiracetam versus placebo on overall survival at D90
3. To evaluate the impact of treatment with levetiracetam versus placebo on duration of mechanical ventilation at D28
4. To evaluate the impact of treatment with levetiracetam versus placebo on length of stay in intensive care and in hospital
5. To evaluate the impact of treatment with levetiracetam versus placebo on occurrence of epileptic seizures from D1 to D14 (EEG or tonic-clonic) and/or occurrence of epileptic abnormalities (periodic epileptic discharges)
6. To evaluate the impact of treatment with levetiracetam versus placebo on time between cessation of sedation and awakening, among patients who did not die under sedation
7. To evaluate the impact of treatment with levetiracetam versus placebo on severity of cognitive impairment at D90, using the T-MoCA (telephone Montreal Cognitive assessment test),
8. To evaluate the impact of treatment with levetiracetam versus placebo on health-related quality of life using the EQ-5D (EUROQOL 5 DIMENSIONS) questionnaire at D90,
9. To evaluate the impact of treatment with levetiracetam versus placebo on autonomy of daily living, using the Katz ADL (Activities of Daily Living) scale at D90
10. To evaluate the impact of treatment with levetiracetam versus placebo on anxiety-depressive state, using the HADS at D90
11. To evaluate the impact of treatment with levetiracetam versus placebo on post-traumatic stress disorder, using the IES-R score at D90

Conditions and MedDRA coding

Adult ICU patients with septic shock

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. age ≥18 years
2. hospitalized in intensive care for less than 96 hours with septic shock evolving for less than 24 hours, defined by : o a clinically or microbiologically documented infection and o a SOFA score ≥2 or an increase in SOFA ≥2 points if organ dysfunction was present prior to infection and o the need for vasopressor administration to maintain a mean arterial pressure ≥65mmHg and o lactatemia > 2mmol/L (18mg/dL) despite adequate vascular filling
3. consent of patient, family member or inclusion in emergency situation without prior consent of patient or family member

Exclusion criteria 15

1. Chronic long-term antiepileptic treatment upon admission or patient with uncontrolled seizures
2. Patients Not affiliated to a social security scheme or CMU
3. Patientswho Participate in another interventional trial with a drug that could interact with levetiracetam or have an impact on the evaluation of the KiSS trial endpoints. In case of doubt, please contact the trial coordinating investigator.
4. Patients with Chronic or progressive central neurological pathologies of traumatic, inflammatory, vascular, infectious, neoplastic or degenerative origin, defined by cognitive impairment not allowing independent living or an IQCODE score > 4.5
5. Patients with Severe head injury less than 3 months old
6. Patients in a situation where active therapies are limited, or for whom the therapeutic commitment is not maximal
7. Patients with Allergy to levetiracetam
8. Minor patients
9. Patients with Pregnancy in progress (bHCG blood or urine)
10. Nursing mothers
11. Patient under guardianship or trusteeship
12. Patient with moderate to severe dementia
13. Patient with psychiatric history and/or suicide attempts
14. Patient presenting a prolonged QTc interval on ECG and/or at risk of cardiovascular disease
15. Concomitant treatment with Methotrexate during the administration of the investigational treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of the KiSS study will be the number of days alive without delirium or coma at D14 following randomization.

Secondary endpoints 11

1. Mortality in intensive care, in hospital, at D28 and D90
2. Overall survival at D90
3. The number of days without mechanical ventilation at D28: the duration between the start and end of mechanical ventilation including invasive, non-invasive mechanical ventilation and high-flow oxygen therapy of the Optiflow™ type (Fisher &. Paykel, Courtabœuf, France). The use of non-invasive ventilation or CPAP for the treatment of sleep apnea or chronic obstructive or restrictive respiratory insufficiency are not taken into account. Translated with DeepL.com (free version)
4. Number of days alive outside the intensive care unit at D28 and outside the hospital at D90
5. Cumulative incidence and type of epileptic seizures between D1 and D14
6. The time between cessation of sedation and awakening
7. Severity of cognitive impairment at D90
8. Severity of anxiety and depression at D90
9. Presence of post-traumatic stress at J90
10. Health-related quality of life at D90
11. Autonomy in daily life at D90

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Shidasp SIAMI

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Dr Shidasp SIAMI

Locations

1 EU/EEA country · 12 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 18 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