Shock, Septic
Conditions
Keywords
Septic Shock
Brief summary
This is a randomized, double-blind, placebo-controlled dose-selection study in which two doses of nangibotide are tested versus placebo.
Detailed description
All patients with a diagnosis of septic shock will be considered for study participation. All potential study patients will receive standard of care for the treatment of septic shock. After screening for eligibility, patients meeting all inclusion and no exclusion criterion will be randomized. Patients will be randomized to one of three treatment arms. Treatment with study drug must be initiated as early as possible, but no later than 24 hours after the onset of septic shock, defined by the start of vasopressor therapy. Patients will be treated for at least 3 days with study drug. After the first 3 days of treatment, patients still requiring vasopressor will be treated until 24 hours after vasopressor withdrawal with a maximum treatment duration of 5 days. Patients will be assessed at the End of Study (EoS) visit at day 28. After the last patient's day 28 visit, the study will be analyzed. Additional follow up (FU) visits will be conducted after 90 days, 6 and 12 months. The objective of the study ist to compare the safety, tolerability and efficacy of two doses of nangibotide versus placebo, when given in addition to standard of care.
Interventions
DRUGnangibotide low dose
nangibotide 0.3 mg/kg/h
DRUGnangibotide high dose
nangibotide 1.0 mg/kg/h
DRUGplacebo
matching placebo
Sponsors
Inotrem
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Provide written informed consent 2. Age 18 to 85 years (inclusive) 3. Documented or suspected infection: lung, abdominal or urinary tract infection (UTI) in the elderly (≥65 years) 4. Organ dysfunction defined as acute change in total SOFA score ≥ 2 points 5. Refractory hypotension requiring vasopressors to maintain MAP ≥65mm Hg despite adequate volume resuscitation 6. Hyperlactatemia (blood lactate \>2 mmol/L or 18 mg/dL).
Exclusion criteria
1. Previous episode of septic shock requiring vasopressor administration within current hospital stay 2. Underlying concurrent immunodepression with anti-CD52 alemtuzumab (Campath) or glucocorticoids \>75 mg prednisone daily or equivalent for more than 7 days 3. Immunosuppressive therapy related to recent (\<6 months) transplantation 4. Cancer chemotherapy (\<3 months) implying an immunodepression 5. Known HIV infection with low CD4 cell count (\<200) for at least 6 months 6. Known pregnancy (positive urine or serum pregnancy test) 7. Shock of any other cause, e.g. hypotension related to gastrointestinal bleeding 8. Ongoing documented or suspected endocarditis, history of prosthetic heart valves 9. Prolonged QT syndrome 10. End-stage neurological disease 11. End-stage cirrhosis (Child Pugh Class C) 12. Acute Physiology and Chronic Health Evaluation (APACHE II) score \<15 or ≥ 34 13. Home oxygen therapy on a regular basis for \> 6 h/day 14. Recent cardiopulmonary resuscitation (CPR) (within current hospital stay) 15. Body mass index (BMI) ≥ 40 kg/m2or weight ≥ 130 kg 16. Moribund patients 17. Decision to limit full care taken before obtaining informed consent 18. Participation in another interventional study in the 3 months prior to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sequential organ failure assessment (SOFA) score | day 5 | Change of total SOFA score from baseline to day 5 (in the subgroup defined by patients with elevated sTREM-1 baseline levels and in the overall population) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of ICU stay | day 28 | hospitalization |
| Organe support free survival | day 28 | time to organe support free |
| Sepsis support index (SSI) | day 28 | Sepsis support index |
| Daily change of total Sequential organ failure assessment (SOFA) score and individual subscores | day 1, day 2, day 3, day 4, day 5, day 6 and day 7 | Daily change of total SOFA score and individual subscores |
| Duration of Vasopressor use | day 28 | Change in the Duration of Vasopressor use |
| Duration of Invasive mechanical ventilation (IMV) | day 28 | Change in the Duration of Invasive mechanical ventilation (IMV) |
| All-cause mortality | day 5 and day 28 | all-cause mortality on D5 and D28 |
| Septic shock related mortality at day 28 | day 28 | mortality caused by septic shock |
| Incidence of secondary infections and post shock antibiotic use | day 28 | Incidence of secondary infections and post shock antibiotic use |
| Alive and organ support free at day 28 | day 28 | Proportion of patients alive and free of organ support at day 28 |
| Overall survival on day 28 | day 28 | time from the date of study drug start to date of death from any cause |
| Overall survival up to 12 months | 12 months | Overall survival up to 12 months |
| Duration of Renal support | day 28 | Change in the Duration of renal replacement therapy, RRT |
Countries
Belgium, Denmark, Finland, France, Ireland, Spain
Outcome results
None listed