Orgaandisfunctie blood poisoning - sepsis
Conditions
Interventions
All patients will be treated according to *International Guidelines for
Management of Severe Sepsis and Septic Shock*.
Eligible patients (confirmed by central verification) will be randomized
(1:1:
patients assigned to the control group will be administered placebo as
intravenous infusion over approximately 1 hour.
As long as the patients are on the ICU, daily measurements of clinical signs
a
Early disease onset
Septic shock
Sponsors
Adrenomed AG
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Written informed consent by patient or legally designated representative (according to country * specific regulations) 2. Male and female patient, age * 18 years 3. Body weight 50 kg * 120 kg 4. Bio-ADM concentration > 70 pg/ml 5. Patient with early septic shock (start of vasopressor therapy
Exclusion criteria
Exclusion criteria: 1. Moribund 2. Pre-existing unstable condition (e.g. a recent cerebral hemorrhage or infarct, a recent acute unstable myocardial infarction (all 30% of body surface 13. Plasmapheresis 14. Breastfeeding women 15. Participation in a clinical trial involving another investigational drug within 4 weeks prior to inclusion 16. Unwilling or unable to be fully evaluated for all follow-up visits
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of this study is * To investigate the safety and tolerability of ADRECIZUMAB in patients with early septic shock and elevated bio-ADM (concentration of > 70 pg/ml) in treatment arm A (2 mg/kg) and in treatment arm B (4 mg/kg) over the 90 days study period. Endpoints for Primary Objective (Safety and Tolerability): The endpoints for the primary objective are to determine over the 90 days study period: * Mortality * Interruption of infusion * Severity and frequency of treatment-emergent adverse events | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary objectives of this study are * To obtain first data on efficacy of ADRECIZUMAB in patients with early septic shock and a bio-ADM concentration of > 70 pg/ml in the treatment arms compared with placebo. * To study the PK of free-ADRECIZUMAB with a focus on plasma accumulation and elimination. Endpoints for Secondary Objective (Efficacy) The primary efficacy endpoint of this study is the * Sepsis Support Index (SSI) defined as: days with organ support or dead within 14 day follow up More precisely: In the time frame of 14 day follow-up, each day on support with vasopressor, and/or mechanical ventilation (defined as any ventilation received on this day, independent from the duration of mechanical ventilation), and/or renal dysfunction (defined as renal SOFA = 4), or not alive, is counted as 1. The sum over the follow up period is defined as SSI. Secondary efficacy endpoints include: * Sepsis Support Index (SSI) at 28 day follow-up * Penalized Sepsis Support Index (pSSI) at 14 and 28 day follow-up, defined similar to the SSI with the exception that patients that die get penalized by assigning the maximum value, i.e. the pSSI is set to 14 or 28, respectively * Persistent organ dysfunction or death at 14 and 28 day follow-up [5] * Day 28 and day 90 mortality rate * SSI and pSSI excluding the renal component * Individual Sepsis Support Index components (hemodynamic, respiratory and renal failure) with and without mortality * Sequential Organ Failure Assessment (SOFA) Score - Mean/maximum/total daily SOFA score during stay at ICU - Delta SOFA score, defined as maximum versus minimum SOFA during ICU stay - Change in SOFA score within 48 hours - SOFA-3 (score limited to cardiovascular, respiratory and renal function) * Improvement in renal function as change in penKid and creatinine (day 3 * day 1, day 7 * day 1) * Duration of stay at ICU/ hospital * Changes of functional parameters and other parameters during stay at ICU (MAP, | — |
Countries
Belgium, France, Germany, Italy, Netherlands
Outcome results
None listed