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 - Full Text View

Purpose

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.

Condition	Intervention	Phase
Severe Sepsis Septic Shock	Drug: AZD9773 Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Sepsis Shock

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Evaluate the effect of 2 different doses of AZD9773 on Ventilator-free days [ Time Frame: Over 28 days following first dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Evaluate the affect of AZD9773 on 7-day mortality in patients with severe sepsis or septic shock [ Time Frame: Over 7 days following first dose ] [ Designated as safety issue: Yes ]
Evaluate the affect of AZD9773 on 28-day mortality in patients with severe sepsis or septic shock [ Time Frame: Over 28 days following first dose ] [ Designated as safety issue: Yes ]
To characterize the safety and tolerability of AZD9773 in patients with severe sepsis or septic shock through the assessment of adverse events, mortality, ECGs, vital signs, laboratory tests, and physical examination [ Time Frame: Over 90 days following first dose ] [ Designated as safety issue: Yes ]

Enrollment:	300
Study Start Date:	October 2010
Estimated Study Completion Date:	May 2012
Estimated Primary Completion Date:	May 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 AZD9773 250/50 units/kg	Drug: AZD9773 A single loading dose following by up to 9 maintenance doses; doses to be given every 12 hours over a period of 5 days Other Name: CytoFab™
Experimental: 2 AZD9773 500/100 units/kg	Drug: AZD9773 A single loading dose following by up to 9 maintenance doses; doses to be given every 12 hours over a period of 5 days Other Name: CytoFab™
Placebo Comparator: 3	Drug: Placebo Placebo

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01145560

Show 52 Study Locations

Sponsors and Collaborators

AstraZeneca

Investigators

Principal Investigator:	Gordon Bernard, MD	Vanderbilt University
Study Director:	Warren Botnick, MD	PAREXEL International
Study Director:	Justin Lindemann, MD	AstraZeneca
Study Director:	Wayne Dankner, MD	PAREXEL International
Study Director:	Jiri Juchelka, MD	PAREXEL International

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01145560 History of Changes
Other Study ID Numbers:	D0620C00003
Study First Received:	June 7, 2010
Last Updated:	March 21, 2012
Health Authority:	United States: Food and Drug Administration Australia: Department of Health and Ageing Therapeutic Goods Administration Belgium: Federal Agency for Medicinal Products and Health Products Canada: Canadian Institutes of Health Research France: Ministry of Health Germany: Federal Institute for Drugs and Medical Devices Spain: Ministry of Health

Keywords provided by AstraZeneca:

severe sepsis
TNF neutralisation
septic shock patients

Additional relevant MeSH terms:

Sepsis
Toxemia
Shock
Shock, Septic

Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on May 22, 2013