Treatment of Patients With Early Septic Shock and Bio-Adrenomedullin(ADM) Concentration > 70 pg/ml With ADRECIZUMAB
Condition: Septic Shock
MeSH terms: Shock, Septic; Shock
Intervention: Adrecizumab; Placebo
Intervention description: Single i.v. dose of 2 mg/kg (treatment arm A) or 4 mg/kg (treatment arm B); Single i.v. dose of placebo (control group)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Double Blind, Placebo-Controlled, Randomized, Multicenter Proof of Concept and Dose-Finding Phase II Clinical Trial
Masking: Double (Participant, Investigator)
Enrollment: 301.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Early Septic Shock

Summary:

      This is a double-blind, placebo-controlled, randomized, multicenter proof of concept and
      dose-finding phase II study using two doses of ADRECIZUMAB in patients with early septic
      shock and a bio-ADM plasma concentration at admission of > 70 pg/ml.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Written informed consent by patient or legal 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 < 12 hours)

          6. Women of childbearing potential must have a negative serum or urine pregnancy test
             before randomization

          7. Highly effective method of contraception must be maintained for 6 months after study
             start by women of childbearing potential and sexually active men.

          8. No care limitation

        Exclusion Criteria:

          1. Moribund

          2. Pre-existing unstable condition (e.g. a recent cerebral hemorrhage or infarct, a
             recent acute unstable myocardial infarction (all < 3 months), congestive heart failure
             - New York Heart Association (NYHA) Class IV

          3. Patients that required cardiopulmonary resuscitation in the last 4 weeks prior to
             evaluation for enrollment

          4. Severe Chronic Obstructive Pulmonary Disease (COPD) with chronic oxygen need at home
             (GOLD IV)

          5. Any organ or bone marrow transplant within the past 24 weeks

          6. Uncontrolled serious hemorrhage (≥ 2 units of blood / platelets in the previous 24
             hrs.). Patients may be considered for enrollment if bleeding has stopped and patient
             is otherwise qualified

          7. Uncontrolled hematological / oncological malignancies

          8. Absolute neutropenia < 500 per µL

          9. Severe chronic liver disease (Child-Pugh C)

         10. Systemic fungal infection or active tuberculosis

         11. Neuromuscular disorders that impact breathing / spontaneous ventilation

         12. Burns > 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