Clinical trial NCT01145560: A Study to Compare the Efficacy and Safety of 2 Dosing Regimens of IV Infusions of AZD9773 (CytoFab™) With Placebo in Adult Patients With Severe Sepsis and/or Septic Shock
Official title: A MultiCentre, Randomized, Double-blind, Placebo-controlled Phase IIb Study to Compare the Efficacy and Safety of Two Dosing Regimens of Intravenous Infusions of AZD9773 (CytoFab™) in Adult Patients With Severe Sepsis and/or Septic Shock
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Severe Sepsis
Septic Shock
Keywords: severe sepsis
TNF neutralisation
septic shock patients
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-06-16
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study to evaluate the effect of two different doses of AZD9773 (CytoFab™) versus placebo on ventilator free days (VFDs) over the first 28 days after the start of dosing with AZD9773 in patients with severe sepsis and/or septic shock, who are already receiving appropriate standard of care treatment for sepsis.


Eligibility criteria: Inclusion Criteria:

* Adults with a first episode of sepsis during this hospitalisation and objective evidence of infection that requires parenteral antibiotics.
* At least 2 of 4 SIRS criteria in the 24 hours before organ dysfunction (must include either fever OR elevated white blood cells \[WBC\])
* Cardiovascular or respiratory dysfunction.

Exclusion Criteria:

* Immunocompromising comorbidities or concomitant medications:

  1. Advanced human immunodeficiency virus (HIV) infection (CD4 ≤50/mm3).
  2. Stage III or IV cancer.
  3. Haemopoietic or lymphoreticular malignancies not in remission.
  4. Receiving radiation therapy or chemotherapy.
  5. Stem cell, organ or bone marrow transplant in the past 6 months.
  6. Absolute neutrophil count \<500 per μL.
  7. High dose steroids or other immunocompromising drugs.
* Concomitant diseases:

  1. Deep seated fungal infection or active tuberculosis.
  2. Cirrhosis with portal hypertension or Childs-Pugh Class C.
  3. History of chronic hypercarbia, respiratory failure in past 6 months or use of home oxygen in the setting of severe chronic respiratory disease.
  4. Neuromuscular disorders that impact breathing/spontaneous ventilation.
  5. Quadriplegia.
  6. Cardiac arrest in the past 30 days.
  7. New York Heart Association functional Class IV due to heart failure or any disorder.
  8. Burns over \> 30% of body surface area.
* Medication and allergy disqualifications.

  1. Treatment with anti-TNF agents within the last 8 weeks.
  2. Previously received ovine derived products (CroFab™, DigiFab™).
  3. Sheep product allergy or allergy to latex, papain, chymopapain.

Primary outcomes:
measure: Ventilator-free Days (VFDs) Over 28 Days
timeFrame: Over 28 days following first dose
Secondary outcomes:
measure: 7-day Mortality
timeFrame: Over 7 days following first dose
measure: 28-day Mortality
timeFrame: Over 28 days following first dose
measure: Safety and Tolerability
timeFrame: All study visits (over 90 days following first dose)
Other outcomes:
Locations:
city: Blacktown
country: Australia
facility: Research Site
state: New South Wales
city: Wollongong
country: Australia
facility: Research Site
state: New South Wales
city: Herston
country: Australia
facility: Research Site
state: Queensland
city: Nambour
country: Australia
facility: Research Site
state: Queensland
city: Woollongabba
country: Australia
facility: Research Site
state: Queensland
city: Adelaide
country: Australia
facility: Research Site
state: South Australia
city: Clayton
country: Australia
facility: Research Site
state: Victoria
city: Footscray
country: Australia
facility: Research Site
state: Victoria
city: Fremantle
country: Australia
facility: Research Site
state: Western Australia
city: Antwerpen
country: Belgium
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Genk
country: Belgium
facility: Research Site
city: Godinne
country: Belgium
facility: Research Site
city: Liege
country: Belgium
facility: Research Site
city: Ottignies
country: Belgium
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Victoria
country: Canada
facility: Research Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Research Site
state: Manitoba
city: Halifax
country: Canada
facility: Research Site
state: Nova Scotia
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Windsor
country: Canada
facility: Research Site
state: Ontario
city: Quebec
country: Canada
facility: Research Site
city: Hradec Kralove
country: Czech Republic
facility: Research Site
city: Praha
country: Czech Republic
facility: Research Site
city: Usti Nad Labem
country: Czech Republic
facility: Research Site
city: Kuopio
country: Finland
facility: Research Site
city: Tampere
country: Finland
facility: Research Site
city: Angers
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: La Roche Sur Yon
country: France
facility: Research Site
city: Limoges
country: France
facility: Research Site
city: Montauban
country: France
facility: Research Site
city: Nantes
country: France
facility: Research Site
city: Nimes
country: France
facility: Research Site
city: Orleans
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Poitiers
country: France
facility: Research Site
city: Saint-michel
country: France
facility: Research Site
city: Toulon
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Tours
country: France
facility: Research Site
city: Vandoeuvre Les Nancy
country: France
facility: Research Site
city: Oviedo
country: Spain
facility: Research Site
state: Asturias
city: Sabadell
country: Spain
facility: Research Site
state: Barcelona
city: Barcelona
country: Spain
facility: Research Site
state: Cataluna
city: Terrassa
country: Spain
facility: Research Site
state: Cataluna
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Santiago de Compostela
country: Spain
facility: Research Site
state: Coruna
city: Palma de Mallorca
country: Spain
facility: Research Site
state: Islas Baleares
city: Getafe
country: Spain
facility: Research Site
state: Madrid
city: Madrid
country: Spain
facility: Research Site
Study officials:
affiliation: Vanderbilt University
name: Gordon Bernard, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Parexel
name: Warren Botnick, MD
role: STUDY_DIRECTOR
affiliation: AstraZeneca
name: Justin Lindemann, MD
role: STUDY_DIRECTOR
affiliation: Parexel
name: Wayne Dankner, MD
role: STUDY_DIRECTOR
affiliation: Parexel
name: Jiri Juchelka, MD
role: STUDY_DIRECTOR
References:
citation: Yates JW, Das S, Mainwaring G, Kemp J. Population pharmacokinetic/pharmacodynamic modelling of the anti-TNF-alpha polyclonal fragment antibody AZD9773 in patients with severe sepsis. J Pharmacokinet Pharmacodyn. 2012 Dec;39(6):591-9. doi: 10.1007/s10928-012-9270-4. Epub 2012 Sep 23.