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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

Primary Purpose

Severe Sepsis, Septic Shock

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

AZD9773

Placebo

About this trial

This is an interventional treatment trial for Severe Sepsis focused on measuring severe sepsis, TNF neutralisation, septic shock patients

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

AZD9773 250/50 units/kg

AZD9773 500/100 units/kg

Outcomes

Primary Outcome Measures

Ventilator-free Days (VFDs) Over 28 Days

Number of ventilator-free days (VFDs)

Secondary Outcome Measures

7-day Mortality

Number of patients who died over 7 days

28-day Mortality

Number of patients who died over 28 days

Safety and Tolerability

Number of patients with treatment-emergent adverse events

Full Information

NCT ID

NCT01145560

First Posted

June 7, 2010

Last Updated

September 26, 2014

Sponsor

AstraZeneca

1. Study Identification

Unique Protocol Identification Number

NCT01145560

Brief Title

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

2. Study Status

Record Verification Date

September 2014

Overall Recruitment Status

Completed

Study Start Date

October 2010 (undefined)

Primary Completion Date

May 2012 (Actual)

Study Completion Date

May 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Severe Sepsis, Septic Shock

Keywords

severe sepsis, TNF neutralisation, septic shock patients

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

300 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

AZD9773 250/50 units/kg

Arm Title

Arm Type

Experimental

Arm Description

AZD9773 500/100 units/kg

Arm Title

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

AZD9773

Other Intervention Name(s)

CytoFab™

Intervention Description

A single loading dose following by up to 9 maintenance doses; doses to be given every 12 hours over a period of 5 days

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo

Primary Outcome Measure Information:

Title

Ventilator-free Days (VFDs) Over 28 Days

Description

Number of ventilator-free days (VFDs)

Time Frame

Over 28 days following first dose

Secondary Outcome Measure Information:

Title

7-day Mortality

Description

Number of patients who died over 7 days

Time Frame

Over 7 days following first dose

Title

28-day Mortality

Description

Number of patients who died over 28 days

Time Frame

Over 28 days following first dose

Title

Safety and Tolerability

Description

Number of patients with treatment-emergent adverse events

Time Frame

All study visits (over 90 days following first dose)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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: 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. High dose steroids or other immunocompromising drugs. 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. 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.

Overall Study Officials: