Please note that the ANZCTR will be unattended from Friday the 17th of July to Monday the 20th of July 2020 inclusive. Thank you and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00604214




Registration number
NCT00604214
Ethics application status
Date submitted
24/01/2008
Date registered
30/01/2008
Date last updated
18/09/2012

Titles & IDs
Public title
Efficacy and Safety of Drotrecogin Alfa (Activated) in Adult Patients With Septic Shock
Scientific title
A Randomized, Double-blind, Placebo-controlled, Multicenter, Phase 3 Study of Drotrecogin Alfa (Activated) Administered as a Continuous 96-hr Infusion to Adult Patients With Septic Shock
Secondary ID [1] 0 0
F1K-MC-EVDP
Secondary ID [2] 0 0
11940
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sepsis 0 0
Condition category
Condition code
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Drotrecogin alfa (activated)
Treatment: Drugs - Placebo

Experimental: Drotrecogin alfa (activated) -

Placebo Comparator: Placebo -


Treatment: Drugs: Drotrecogin alfa (activated)
24 microgram/kilogram/hour, intravenous, 96 hours (hr)

Treatment: Drugs: Placebo
0.9% sodium chloride, intravenous, 96 hours

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
28-Day All-Cause Mortality - Expressed as percentage of participants who died from any cause at Day 28 endpoint.
Timepoint [1] 0 0
Day 28
Secondary outcome [1] 0 0
28-Day All-Cause Mortality in Participants With Severe Protein C Deficiency - Expressed as percentage of participants who died from any cause at Day 28 endpoint. Participants with severe protein C deficiency are those who had a protein C level = half the lower limit of normal (LLN) (=40%).
Timepoint [1] 0 0
Day 28
Secondary outcome [2] 0 0
Average Cardiovascular Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 - Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing cardiovascular dysfunction. A non-surviving participant receives a score of 4 (worst score) for the day of death and every day thereafter.
Timepoint [2] 0 0
Day 1 through Day 28
Secondary outcome [3] 0 0
Average Respiratory Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 - Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing respiratory dysfunction. A non-surviving participant receives a score of 4 (worst score) for the day of death and every day thereafter.
Timepoint [3] 0 0
Day 1 through Day 28
Secondary outcome [4] 0 0
Average Renal Sequential Organ Failure Assessment (SOFA) Score Day 1 Through Day 28 - Scores range from 0 (normal) to 4 (organ failure) with an increasing score indicating increasing renal dysfunction. A non-surviving participant receives a score of 4 (worst score) for the day of death and every day thereafter.
Timepoint [4] 0 0
Day 1 through Day 28
Secondary outcome [5] 0 0
90-Day Mortality - Expressed as percentage of participants who died from any cause at Day 90 endpoint.
Timepoint [5] 0 0
Day 90
Secondary outcome [6] 0 0
180-Day Mortality - Expressed as percentage of participants who died from any cause at Day 180 endpoint.
Timepoint [6] 0 0
Day 180
Secondary outcome [7] 0 0
Median Survival Time
Timepoint [7] 0 0
Day 180
Secondary outcome [8] 0 0
EuroQoL Questionnaire-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) Scores at Baseline, Days 28, 90 and 180 - EQ-5D VAS assesses caregiver's impression of participant's overall health state. Scores range from 0 (worst health state) to 100 (best health state), with higher scores indicating a better health state.
Timepoint [8] 0 0
Baseline and Days 28 and 90 and 180
Secondary outcome [9] 0 0
EuroQoL Questionnaire-5 Dimensions (EQ-5D) Total Scores at Baseline, Days 28, 90 and 180 - The EQ-5D is used to assess participant's overall health. Consists of 5 items: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each item has 3 severity levels (no, some, severe problems). Calculated from EQ-5D, total scores (United States [US] Index Score) range from 0 (worst quality of life) to 1.00 (best quality of life).
Timepoint [9] 0 0
Baseline and Days 28 and 90 and 180
Secondary outcome [10] 0 0
Quality of Life Short Form-12 (SF-12) Scores at Baseline, Days 28, 90 and 180 - SF-12 was used as an instrument to measure participants' physical wellbeing (physical component) and mental wellbeing (mental component). Scores for each component range from 0-100, with 0= lowest wellbeing, and 100=highest wellbeing.
Timepoint [10] 0 0
Baseline and Days 28 and 90 and 180
Secondary outcome [11] 0 0
Percentage of Participants Discontinued Due to Adverse Events Any Time From Baseline Through Day 28 Endpoint
Timepoint [11] 0 0
Baseline through Day 28

Eligibility
Key inclusion criteria
- Must be 18 years or older

- Must have evidence of infection

- Must have systemic inflammatory response syndrome (SIRS)

- Must have vasopressor-dependent septic shock
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Have received vasopressor therapy (at any dose) for greater than 24 hours prior to the
start of study drug

- Have sepsis-induced organ dysfunction for greater than 36 hours prior to the start of
the study drug infusion

- Have single organ dysfunction and recent surgery (within 30 days of study entry)

- Have had surgery performed within the 12-hour period immediately preceding the study
drug infusion, or are postoperative with evidence of active bleeding, or have planned
or anticipated surgery during the infusion period

- Are not expected to survive 28 days given their preexisting uncorrectable medical
condition

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Garran
Recruitment hospital [2] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Newcastle
Recruitment hospital [3] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - St. Leonards
Recruitment hospital [4] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Herston
Recruitment hospital [5] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Adelaide
Recruitment hospital [6] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Box Hill
Recruitment hospital [7] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Epping
Recruitment hospital [8] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Heidelberg
Recruitment hospital [9] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Melbourne
Recruitment hospital [10] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Parkville
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2305 - Newcastle
Recruitment postcode(s) [3] 0 0
2065 - St. Leonards
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment postcode(s) [6] 0 0
3128 - Box Hill
Recruitment postcode(s) [7] 0 0
3076 - Epping
Recruitment postcode(s) [8] 0 0
3084 - Heidelberg
Recruitment postcode(s) [9] 0 0
3004 - Melbourne
Recruitment postcode(s) [10] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Idaho
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
Montana
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Oregon
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Virginia
Country [18] 0 0
Belgium
State/province [18] 0 0
Antwerpen
Country [19] 0 0
Belgium
State/province [19] 0 0
Antwerp
Country [20] 0 0
Belgium
State/province [20] 0 0
Brussels
Country [21] 0 0
Belgium
State/province [21] 0 0
Edegem
Country [22] 0 0
Belgium
State/province [22] 0 0
Genk
Country [23] 0 0
Belgium
State/province [23] 0 0
Leuven
Country [24] 0 0
Belgium
State/province [24] 0 0
Liège
Country [25] 0 0
Belgium
State/province [25] 0 0
Ottignies
Country [26] 0 0
Belgium
State/province [26] 0 0
Roeselare
Country [27] 0 0
Belgium
State/province [27] 0 0
Wilrijk
Country [28] 0 0
Belgium
State/province [28] 0 0
Yvoir
Country [29] 0 0
Brazil
State/province [29] 0 0
Belo Horizonte
Country [30] 0 0
Brazil
State/province [30] 0 0
Joinville
Country [31] 0 0
Brazil
State/province [31] 0 0
Londrina
Country [32] 0 0
Brazil
State/province [32] 0 0
Porto Alegre
Country [33] 0 0
Brazil
State/province [33] 0 0
Sao Jose Rio Preto
Country [34] 0 0
Brazil
State/province [34] 0 0
São Paulo
Country [35] 0 0
Canada
State/province [35] 0 0
Alberta
Country [36] 0 0
Canada
State/province [36] 0 0
British Columbia
Country [37] 0 0
Canada
State/province [37] 0 0
Manitoba
Country [38] 0 0
Canada
State/province [38] 0 0
Ontario
Country [39] 0 0
Canada
State/province [39] 0 0
Quebec
Country [40] 0 0
Czech Republic
State/province [40] 0 0
Brno
Country [41] 0 0
Czech Republic
State/province [41] 0 0
Hradec Kralove
Country [42] 0 0
Czech Republic
State/province [42] 0 0
Olomouc
Country [43] 0 0
Czech Republic
State/province [43] 0 0
Plzen
Country [44] 0 0
Czech Republic
State/province [44] 0 0
Prague
Country [45] 0 0
Czech Republic
State/province [45] 0 0
Usti Nad Labem
Country [46] 0 0
Finland
State/province [46] 0 0
Helsinki
Country [47] 0 0
Finland
State/province [47] 0 0
Jyvaskyla
Country [48] 0 0
Finland
State/province [48] 0 0
Kuopio
Country [49] 0 0
Finland
State/province [49] 0 0
Lahti
Country [50] 0 0
Finland
State/province [50] 0 0
Seinajoki
Country [51] 0 0
Finland
State/province [51] 0 0
Tampere
Country [52] 0 0
France
State/province [52] 0 0
Angers
Country [53] 0 0
France
State/province [53] 0 0
Argenteuil
Country [54] 0 0
France
State/province [54] 0 0
Bobigny
Country [55] 0 0
France
State/province [55] 0 0
Bordeaux
Country [56] 0 0
France
State/province [56] 0 0
Dijon
Country [57] 0 0
France
State/province [57] 0 0
La Roche Sur Yon
Country [58] 0 0
France
State/province [58] 0 0
Le Kremlin Bicetre
Country [59] 0 0
France
State/province [59] 0 0
Limoges
Country [60] 0 0
France
State/province [60] 0 0
Lyon
Country [61] 0 0
France
State/province [61] 0 0
Montpellier
Country [62] 0 0
France
State/province [62] 0 0
Nantes
Country [63] 0 0
France
State/province [63] 0 0
Nice
Country [64] 0 0
France
State/province [64] 0 0
Nimes
Country [65] 0 0
France
State/province [65] 0 0
Paris
Country [66] 0 0
France
State/province [66] 0 0
Poissy
Country [67] 0 0
France
State/province [67] 0 0
Poitiers
Country [68] 0 0
France
State/province [68] 0 0
Pringy
Country [69] 0 0
France
State/province [69] 0 0
Rennes
Country [70] 0 0
France
State/province [70] 0 0
Saint Michel
Country [71] 0 0
France
State/province [71] 0 0
Saint-Etienne
Country [72] 0 0
France
State/province [72] 0 0
Toulon
Country [73] 0 0
France
State/province [73] 0 0
Tours
Country [74] 0 0
France
State/province [74] 0 0
Vandoeuvre-Les-Nancy
Country [75] 0 0
Germany
State/province [75] 0 0
Aachen
Country [76] 0 0
Germany
State/province [76] 0 0
Augsburg
Country [77] 0 0
Germany
State/province [77] 0 0
Berlin
Country [78] 0 0
Germany
State/province [78] 0 0
Gottingen
Country [79] 0 0
Germany
State/province [79] 0 0
Hamburg
Country [80] 0 0
Germany
State/province [80] 0 0
Heidelberg
Country [81] 0 0
Germany
State/province [81] 0 0
Kiel
Country [82] 0 0
Germany
State/province [82] 0 0
Munich
Country [83] 0 0
India
State/province [83] 0 0
Bangalore
Country [84] 0 0
India
State/province [84] 0 0
New Delhi
Country [85] 0 0
India
State/province [85] 0 0
Pune
Country [86] 0 0
Italy
State/province [86] 0 0
Catania
Country [87] 0 0
Italy
State/province [87] 0 0
Firenze
Country [88] 0 0
Italy
State/province [88] 0 0
Milano
Country [89] 0 0
Italy
State/province [89] 0 0
Monza
Country [90] 0 0
Italy
State/province [90] 0 0
Novara
Country [91] 0 0
Italy
State/province [91] 0 0
Padova
Country [92] 0 0
Italy
State/province [92] 0 0
Rome
Country [93] 0 0
Italy
State/province [93] 0 0
Torino
Country [94] 0 0
Italy
State/province [94] 0 0
Varese
Country [95] 0 0
Mexico
State/province [95] 0 0
Mexico City
Country [96] 0 0
Mexico
State/province [96] 0 0
Tlalpan
Country [97] 0 0
Netherlands
State/province [97] 0 0
Arnhem
Country [98] 0 0
Netherlands
State/province [98] 0 0
Ede
Country [99] 0 0
Netherlands
State/province [99] 0 0
Nijmegen
Country [100] 0 0
New Zealand
State/province [100] 0 0
Auckland
Country [101] 0 0
New Zealand
State/province [101] 0 0
Christchurch
Country [102] 0 0
New Zealand
State/province [102] 0 0
Grafton
Country [103] 0 0
New Zealand
State/province [103] 0 0
Hamilton
Country [104] 0 0
New Zealand
State/province [104] 0 0
Wellington
Country [105] 0 0
Portugal
State/province [105] 0 0
Lisbon
Country [106] 0 0
Portugal
State/province [106] 0 0
Porto
Country [107] 0 0
Spain
State/province [107] 0 0
Alcala De Henares
Country [108] 0 0
Spain
State/province [108] 0 0
Barcelona
Country [109] 0 0
Spain
State/province [109] 0 0
Burgos
Country [110] 0 0
Spain
State/province [110] 0 0
Getafe
Country [111] 0 0
Spain
State/province [111] 0 0
Las Palmas
Country [112] 0 0
Spain
State/province [112] 0 0
Madrid
Country [113] 0 0
Spain
State/province [113] 0 0
Murcia
Country [114] 0 0
Spain
State/province [114] 0 0
Palma De Mallorca
Country [115] 0 0
Spain
State/province [115] 0 0
Sabadell
Country [116] 0 0
Spain
State/province [116] 0 0
Sevilla
Country [117] 0 0
Spain
State/province [117] 0 0
Tortosa
Country [118] 0 0
Spain
State/province [118] 0 0
Valladolid
Country [119] 0 0
Switzerland
State/province [119] 0 0
Lugano
Country [120] 0 0
Switzerland
State/province [120] 0 0
St Gallen
Country [121] 0 0
Switzerland
State/province [121] 0 0
Zurich
Country [122] 0 0
United Kingdom
State/province [122] 0 0
Avon
Country [123] 0 0
United Kingdom
State/province [123] 0 0
Devon
Country [124] 0 0
United Kingdom
State/province [124] 0 0
Essex
Country [125] 0 0
United Kingdom
State/province [125] 0 0
Hampshire
Country [126] 0 0
United Kingdom
State/province [126] 0 0
Hants
Country [127] 0 0
United Kingdom
State/province [127] 0 0
Scotland
Country [128] 0 0
United Kingdom
State/province [128] 0 0
Surrey
Country [129] 0 0
United Kingdom
State/province [129] 0 0
West Midlands
Country [130] 0 0
United Kingdom
State/province [130] 0 0
West Sussex
Country [131] 0 0
United Kingdom
State/province [131] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this placebo-controlled study is to determine if drotrecogin alfa (activated)
treatment provides significant mortality reduction improvement in patients with septic shock
compared with placebo treatment in patients receiving the current standard of care for septic
shock. This study will also assess the effectiveness of drotrecogin alfa (activated) in
reducing 28-day mortality in patients with septic shock and concomitant severe protein C
deficiency.
Trial website
https://clinicaltrials.gov/show/NCT00604214
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications