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

Septic Shock Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01145560
• Other study ID #: D0620C00003
• Status: Completed
• Phase: Phase 2
• First received: June 7, 2010
• Last updated: September 26, 2014
• Start date: October 2010
• Est. completion date: May 2012

Study information

• Verified date: September 2014
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsCanada: Canadian Institutes of Health ResearchFrance: Ministry of HealthGermany: Federal Institute for Drugs and Medical DevicesSpain: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Severe Sepsis
• Shock
• Shock, Septic
• Toxemia

Intervention

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
• Placebo
Placebo

Locations

Country	Name	City	State
Australia	Research Site	Adelaide	South Australia
Australia	Research Site	Blacktown	New South Wales
Australia	Research Site	Clayton	Victoria
Australia	Research Site	Footscray	Victoria
Australia	Research Site	Fremantle	Western Australia
Australia	Research Site	Herston	Queensland
Australia	Research Site	Nambour	Queensland
Australia	Research Site	Wollongong	New South Wales
Australia	Research Site	Woollongabba	Queensland
Belgium	Research Site	Antwerpen
Belgium	Research Site	Brussels
Belgium	Research Site	Genk
Belgium	Research Site	Godinne
Belgium	Research Site	Liege
Belgium	Research Site	Ottignies
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Vancouver	British Columbia
Canada	Research Site	Victoria	British Columbia
Canada	Research Site	Windsor	Ontario
Canada	Research Site	Winnipeg	Manitoba
Czech Republic	Research Site	Hradec Kralove
Czech Republic	Research Site	Praha
Czech Republic	Research Site	Usti Nad Labem
Finland	Research Site	Kuopio
Finland	Research Site	Tampere
France	Research Site	Angers
France	Research Site	Dijon
France	Research Site	La Roche Sur Yon
France	Research Site	Limoges
France	Research Site	Montauban
France	Research Site	Nantes
France	Research Site	Nimes
France	Research Site	Orleans
France	Research Site	Paris
France	Research Site	Poitiers
France	Research Site	Saint-michel
France	Research Site	Toulon
France	Research Site	Toulouse
France	Research Site	Tours
France	Research Site	Vandoeuvre Les Nancy
Spain	Research Site	Barcelona	Cataluna
Spain	Research Site	Getafe	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Oviedo	Asturias
Spain	Research Site	Palma de Mallorca	Islas Baleares
Spain	Research Site	Sabadell	Barcelona
Spain	Research Site	Santiago de Compostela	Coruna
Spain	Research Site	Terrassa	Cataluna
Spain	Research Site	Valencia	Comunidad Valenciana

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Australia,  Belgium,  Canada,  Czech Republic,  Finland,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ventilator-free Days (VFDs) Over 28 Days	Number of ventilator-free days (VFDs)	Over 28 days following first dose	No
Secondary	7-day Mortality	Number of patients who died over 7 days	Over 7 days following first dose	Yes
Secondary	28-day Mortality	Number of patients who died over 28 days	Over 28 days following first dose	Yes
Secondary	Safety and Tolerability	Number of patients with treatment-emergent adverse events	All study visits (over 90 days following first dose)	Yes

External Links

•   CSR-D0620C00003.pdf
•   redacted-CSP-D0620C00003.pdf