Severe SepsisPhase 2NCT01145560

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

A Phase 2 study testing AZD9773 in people with Severe Sepsis and Septic Shock, run by AstraZeneca at 52 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Severe Sepsis, Septic Shock
What is being tested?: AZD9773
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 300 participants
Where: 52 sitesin 7 countries
Study dates: Oct 2010to May 2012
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 21Show fewer

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.

Trial locations and contacts

52 sites in 7 countries.

Country

City, postcode or hospital

52 sites in 7 countries

France15 sites

Research Site
Angers
Research Site
Dijon
Research Site
La Roche-sur-Yon
Research Site
Limoges
Research Site
Montauban
Research Site
Nantes
Research Site
Nîmes
Research Site
Orléans
Research Site
Paris
Research Site
Poitiers
Research Site
Saint-Michel
Research Site
Toulon
Research Site
Toulouse
Research Site
Tours
Research Site
Vandœuvre-lès-Nancy

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Australia9 sites

Research Site
Adelaide, South Australia
Research Site
Blacktown, New South Wales
Research Site
Clayton, Victoria
Research Site
Footscray, Victoria
Research Site
Fremantle, Western Australia
Research Site
Herston, Queensland
Research Site
Nambour, Queensland
Research Site
Wollongong, New South Wales
Research Site
Woollongabba, Queensland

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Spain9 sites

Research Site
Barcelona, Catalonia
Research Site
Getafe, Madrid
Research Site
Madrid, Madrid
Research Site
Oviedo, Principality of Asturias
Research Site
Palma de Mallorca, Balearic Islands
Research Site
Sabadell, Barcelona
Research Site
Santiago de Compostela, Coruna
Research Site
Terrassa, Catalonia
Research Site
Valencia, Valencia

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Canada8 sites

Research Site
Edmonton, Alberta
Research Site
Halifax, Nova Scotia
Research Site
Ottawa, Ontario
Research Site
Québec, Quebec
Research Site
Vancouver, British Columbia
Research Site
Victoria, British Columbia
Research Site
Windsor, Ontario
Research Site
Winnipeg, Manitoba

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Belgium6 sites

Research Site
Antwerp, Belgium
Research Site
Brussels, Belgium
Research Site
Genk, Belgium
Research Site
Godinne, Belgium
Research Site
Liège, Belgium
Research Site
Ottignies, Belgium

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Czechia3 sites

Research Site
Hradec Králové
Research Site
Prague
Research Site
Ústí nad Labem

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Finland2 sites

Research Site
Kuopio
Research Site
Tampere

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About this study

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

Conditions: Severe Sepsis, Septic Shock
Being tested: AZD9773, Placebo
Keywords: severe sepsis, TNF neutralisation, septic shock patients
Medical subject headings: Sepsis, Shock, Septic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AZD9773Drug
Also called CytoFab™
A single loading dose following by up to 9 maintenance doses; doses to be given every 12 hours over a period of 5 days
PlaceboDrug
Placebo

Study groups in NCT01145560
Study group	Role	What they receive
1	Experimental	AZD9773 250/50 units/kg Receives: Drug: AZD9773
2	Experimental	AZD9773 500/100 units/kg Receives: Drug: AZD9773
3	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Ventilator-free Days (VFDs) Over 28 Days
Number of ventilator-free days (VFDs)
Measured: Over 28 days following first dose

Secondary outcomes (3)

7-day Mortality
Number of patients who died over 7 days
Measured: Over 7 days following first dose
28-day Mortality
Number of patients who died over 28 days
Measured: Over 28 days following first dose
Safety and Tolerability
Number of patients with treatment-emergent adverse events
Measured: All study visits (over 90 days following first dose)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2010May 2012

First posted16 Jun 2010 (estimated)
Study startOct 2010
Primary completionMay 2012
Study completionMay 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Severe SepsisStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 300 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01145560
Sponsor's protocol ID: D0620C00003
Status last verified: Sep 2014
First submitted: 7 Jun 2010
Last updated: 6 Oct 2014
Results posted: Yes, on ClinicalTrials.gov

Publications

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.
PubMed 23001587

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 6 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01145560
Acronym / sponsor ID: D0620C00003
Conditions: Severe Sepsis, Septic Shock
Keywords: severe sepsis, TNF neutralisation, septic shock patients
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 300 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Oct 2010
Primary completion: May 2012 (actual)
Study completion: May 2012 (actual)
First posted: 16 Jun 2010 (estimated)
Results: Posted 23 Sep 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 3

Arm	Type	Receives
1	Experimental	Drug: AZD9773AZD9773 250/50 units/kg
2	Experimental	Drug: AZD9773AZD9773 500/100 units/kg
3	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (21 listed)

Immunocompromising comorbidities or concomitant medications:
Concomitant diseases:
Medication and allergy disqualifications.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AZD9773Also: CytoFab™A single loading dose following by up to 9 maintenance doses; doses to be given every 12 hours over a period of 5 days	Drug	1, 2
PlaceboPlacebo	Drug	3

Primary outcome

Ventilator-free Days (VFDs) Over 28 Days
Time frame: Over 28 days following first dose
Number of ventilator-free days (VFDs)

3 secondary outcomes

7-day Mortality
Time frame: Over 7 days following first dose
28-day Mortality
Time frame: Over 28 days following first dose
Safety and Tolerability
Time frame: All study visits (over 90 days following first dose)

Results and safety

Results posted to the registry on 23 Sep 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AZD9773 250/50 Units/kg	100	96
AZD9773 500/100 Units/kg	100	96
Placebo	100	98

Primary outcome: Ventilator-free Days (VFDs) Over 28 Days

Time frame: Over 28 days following first dose. Median (Full Range). Unit: Days

Measure	AZD9773 250/50 Units/kg n = 100	AZD9773 500/100 Units/kg n = 100	Placebo n = 100
Value	21.0 (0 to 28)	17.5 (0 to 28)	19.0 (0 to 28)

Population analysed: Intention-to-treat analysis set

3 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
AZD9773 250/50 Units/kg	28 of 100 (28%)	74 of 100 (74%)	Not reported
AZD9773 500/100 Units/kg	27 of 97 (27.8%)	71 of 97 (73.2%)	Not reported
Placebo	31 of 99 (31.3%)	68 of 99 (68.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23001587Yates 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.
CSR-D0620C00003.pdfLink provided by the sponsor.
redacted-CSP-D0620C00003.pdfLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gordon Bernard, MD principal investigator

Vanderbilt University

Warren Botnick, MD study director

Parexel

Justin Lindemann, MD study director

AstraZeneca

52 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AZD9773 in people with Severe Sepsis and Septic Shock, run by AstraZeneca at 52 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 52 sites in France, Australia, Spain, Canada, Belgium and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Sep 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ventilator-free Days (VFDs) Over 28 Days (time frame: Over 28 days following first dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01145560, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2014.