Intensive care - septic shock Blood infection
Conditions
Interventions
Stage 1 is investigating multiple ascending doses of MOTREM or placebo in a
sequential design in cohorts of 4 patients (3:1 randomisation).
Stage 2 investigates 3 doses of MOTREM in a randomised, ba
MOTREM (LR12)
Septic Shock
Sponsors
INOTREM S.A
Eligibility
Age
12 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Provide written informed consent (proxy/legal representative/independent physician/emergency consent) according to local regulations 2. Age 18* to 80 years * 16 to 80 years in the Netherlands Sepsis 3. Documented or suspected infection: lung, abdominal or elderly UTI (*65 years) 4. Organ dysfunction defined as acute change in SOFA score * 2 points Shock 5. Refractory hypotension requiring vasopressors to maintain MAP *65mm Hg despite adequate volume resuscitation of at least 20 ml/kg within 6 hours (according to Surviving Sepsis guidelines, see Appendix 1) 6. Hyperlactatemia (blood lactate >2 mmol/l or 18 mg/dl). This criterion must be met at least once for the purpose of diagnosis within the 24 hours before study drug administration
Exclusion criteria
Exclusion criteria: 1. Previous episode of septic shock (vasopressor administration) within current hospital stay 2. Underlying concurrent immunodepression (specified in appendix 2) 3. Solid organ transplant requiring immunosuppressive therapy 4. Known pregnancy (positive serum pregnancy test) 5. Prolonged QT syndrome (QTc * 440 ms) 6. Shock of any other cause, e.g. hypotension related to gastrointestinal bleeding 7. Ongoing documented or suspected endocarditis, history of prosthetic heart valves 8. End-stage neurological disease 9. End-stage cirrhosis (Child Pugh Class C) 10. Acute Physiology And Chronic Health Evaluation (APACHE) II score * 34 11. End stage chronic renal disease requiring chronic dialysis 12. Home oxygen therapy on a regular basis for > 6 h/day 13. Severe obesity (BMI * 40) 14. Recent CPR (within current hospital stay) 15. Moribund patients 16. Decision to limit full care taken before obtaining informed consent 17. Participation in another interventional study in the 3 months prior to randomisation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability parameters: 1. Vital signs: systolic (SBP) and diastolic (DBP) blood pressure, heart rate, and body temperature (tympanic) 2. ECG (12-lead ECG) 3. Safety laboratory tests: haematology, coagulation, plasma biochemistry 4. Presence of anti-LR12 antibodies 5. Adverse events : from screening until study completion | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Plasma concentrations of LR12 will be measured by a validated LCMS/MS assay and analysed using non-compartmental methods to obtain estimates of the PK parameters. Pharmacodynamics (exploratory) The concentration profiles of biomarkers (sTREM-1, immune and vascular related biomarkers) over time and biomarker mRNA levels will be analysed. Clinical parameters (exploratory) 1. Resolution of organ dysfunction (SOFA score total and individual domains) 2. Vasopressor use 3. Invasive mechanical ventilation 4. Renal support 5. Time until shock reversal defined as cessation of vasopressor support for 24 hours 6. Mortality at day 28 and Day 90 | — |
Countries
Belgium, France, Netherlands, Spain
Outcome results
None listed