A Multicentre, Randomised, Double Blind, Placebo controlled Phase IIb Study to compare the Efficacy and Safety of Two Dosing Regimens of Intravenous Infusions of CytoFab™ (AZD9773) in Adult Patients With Severe Sepsis and/or Septic Shock
- Conditions
- Severe sepsis and/or septic shockMedDRA version: 12.1Level: LLTClassification code 10040047Term: Sepsis
- Registration Number
- EUCTR2009-015168-32-CZ
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 300
1. Adults with a first episode of sepsis during this hospitalisation.
2. Objective clinical evidence of infection.
3. At least 2 of 4 SIRS criteria in the 24 hours before organ dysfunction (must include
either fever OR elevated white blood cells [WBC]).
4. Cardiovascular and/or respiratory dysfunction.
Note: complete details are listed in Section 5.1 of the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Moribund (not likely to survive 24 hours) or significant comorbidities making
survival for 3 months unlikely.
2. Immunocompromising comorbidities or concomitant medications.
•Advanced human immunodeficiency virus (HIV) infection (CD4 =50/mm3).
•Stage III or IV cancer.
•Haemopoietic or lymphoreticular malignancies not in remission.
•Receiving radiation therapy or chemotherapy.
•Stem cell, organ or bone marrow transplant in the past 6 months.
•Absolute neutrophil count <500 per µL.
•Doses of some steroids and some immunocompromising drugs.
3. Concomitant diseases:
•Deep seated fungal infection or active tuberculosis.
•Cirrhosis with portal hypertension or Childs-Pugh Class C.
•History of chronic hypercarbia, respiratory failure in past 6 months or use of
•home oxygen in the setting of severe chronic respiratory disease.
•Neuromuscular disorders that impact breathing/spontaneous ventilation.
•Quadriplegia.
•Cardiac arrest in the past 30 days.
•New York Heart Association functional Class IV due to heart failure or any disorder.
•Burns over > 30% of body surface area.
4. Medication and allergy disqualifications.
•Treatment with anti-TNF agents within the last 8 weeks.
•Previously received ovine derived products (CroFab™, DigiFab™).
•Sheep product allergy or allergy to latex, papain, chymopapain.
5. Pregnancy or plans to breast feed upon resolution of sepsis.
Note: complete details are listed in Section 5.2 of the protocol.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to evaluate the effect of two different doses of AZD9773 (CytoFab™) versus placebo on ventilator free days (VFDs) over 28 days in patients with severe sepsis and/or septic shock, who are receiving appropriate standard of care.<br>;Primary end point(s): Ventilator free days over the 28 day study period;Secondary Objective: The secondary objectives are to evaluate the effect of two different doses of AZD9773 versus placebo in patients with severe sepsis and/or septic shock on 7 day and 28 day mortality, the safety profile, morbidity,mortality at Day 90, health related Quality of Life (QoL) and the biological effect on plasma tumour necrosis factor alfa (TNFa) levels and relevant cytokines. There will also be an attempt to determine the population pharmacokinetics (PK) of AZD9773 and to assess the relationship between PK and measures of pharmacodynamic (PD) response, efficacy and adverse events (AEs) in patients with severe sepsis and/or septic shock.<br>
- Secondary Outcome Measures
Name Time Method