To demonstrate that treatment with drotrecogin alfa (activated) 24 mcg/kg/h administered as an intravenous infusion for 96 hours reduces 28 day all-cause mortality in adult patients with septic shock compared with placebo.
ID
Source
Brief title
Condition
- General system disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
All-cause mortalilty after 28 days
Secondary outcome
1. Death related to severe sepsis, that is, related to severe sepsis or a
sequela of sepsis based on the interpretation of the investigator.
2. Cardiovascular events: the need for vasoactive drugs or hypotension.
3. Respiratory events: decreased PaO2/FiO2, mechanical ventilation, hypoxia,
acute respiratory distress syndrome, acute lung injury, or respiratory failure.
4. Hepatic events: hepatic injury or liver dysfunction that leads to an
increase from baseline in the serum level of bilirubin.
5. Renal events: renal failure, renal insufficiency, or renal injury that leads
to an increase from baseline in serum creatinine.
6. Hematologic/coagulation events: coagulopathy, disseminated intravascular
coagulation, thrombocytopenia, or thrombocytosis.
7. Systemic inflammatory response syndrome related criteria: tachypnea,
hypopnea, leukocytosis, leukopenia, hypothermia, hyperthermia, tachycardia, or
bradycardia.
Background summary
Page 15 and 16 of the study protocol:
Septic shock as an independent criterion for the use of drotregocin alfa
(activated) has not been studied in previous trials. Drotregocin alfa
(activated) received approval on the basis of a study in patients with severe
shock (PROWESS). Since registration, two placebo-controlled studies of
drotegocin alfa (activated) have not shown evidence of efficacy. The EMEA have
requested the sponsor, Eli Lilly,an additional placebo-controlled study to
further evaluate the efficacy and safety of drotrecogin alfa (activated) and to
better identify patients who would benefit from drotrecogin alfa (activated)
treatment.
Study objective
To demonstrate that treatment with drotrecogin alfa (activated) 24 mcg/kg/h
administered as an intravenous infusion for 96 hours reduces 28 day all-cause
mortality in adult patients with septic shock compared with placebo.
Study design
A multicenter, randomized, double-blind, parallel, placebo controlled, Phase 3
study of drotrecogin alfa (activated) in patients with septic shock. Planned
enrollment in the study is approximately 1500 patients. Patients will be
randomly assigned to either the drotrecogin alfa (activated) or placebo
treatment group in a 1:1 ratio. Randomization will be stratified by
investigative site. The study consists of 4 treatment periods: pretreatment,
treatment, post treatment, and follow-up
Intervention
Subjects will be randomly assigned to either drotrecogin alfa (activated) 24
mcg/kg/h administered as an intravenous infusion for 96 hours or to placebo.
Study burden and risks
In order to enroll eligible patients and to monitor their safety, the Vandebilt
coordinating centre (VCC) is contracted to support the investigative sites.
The VCC will be consulted by the study team at the sites to confirm eligibility
of each patient for inclusion in the study. The VCC will also be notified by
the sites of all SAEs. This will need to be done within 24 hours that the
investigator was aware of the SAE. VCC will process all initial SAEs per
protocol criteria on forms provided by Parexel.
The patient is at no greater risk than with the standard treatment he/she would
receive
Pharmaco-genetic substudy: Participation is voluntary and is not a prerequisite
for participation in the study. In total, four bloodsamples ( two before the
start of the study drug infusion, one sample on day one and one sample on day
four after starting the study drug infusion) will be taken from those patients
who have signed the separate pharmaco-genetic patient information form.
Erl Wood Manor, Sunninghill Road
Windlesham, Surrey, GU20 6PH
GB
Erl Wood Manor, Sunninghill Road
Windlesham, Surrey, GU20 6PH
GB
Listed location countries
Age
Inclusion criteria
1. Patient must be an adult (18 years or older)
2. Patient must have evidence of an infection for which the patient is receiving intravenous antimicrobial therapy
3. Patient must have systemic inflammatory response syndrome (SIRS).
4. Patient must have septic shock
5. Patients must remain vasopressor dependent throughout the pretreatment period and through the time of randomization
Exclusion criteria
Patients who, prior to the start of study drug, have received vasopressor therapy (at any dose) for greater than 24 hours or have sepsis-induced organ dysfunction for greater than 36 hours, patients who have had surgery performed within the 12-hour period immediately preceding the study drug infusion, have an active internal bleeding or are at increased risk for bleeding, patients who are not expected to survive 28 days given their preexisting uncorrectable medical condition or are receiving concommitant therapies that will have an impact on their wellbeing
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-005441-38-NL |
| CCMO | NL21012.091.07 |