to Determine Efficacy and Safety of Extended Drotrecogin Alfa (Activated) Therapy in Patients With Persistent Requirement for Vasopressor Support After 96-Hour Infusion With Commercial Drotrecogin Alfa (Activated

• Register: EUCTR
• Last refreshed on: 19 April 2022
• Main ID: EUCTR2004-001319-71-ES
• Date of registration: 13/04/2012
• Prospective Registration: No
• Primary sponsor: Lilly S.A.
• Public title: to Determine Efficacy and Safety of Extended Drotrecogin Alfa (Activated) Therapy in Patients With Persistent Requirement for Vasopressor Support After 96-Hour Infusion With Commercial Drotrecogin Alfa (Activated
• Scientific title: A Phase IIIb Study to Determine Efficacy and Safety of Extended Drotrecogin Alfa (Activated) Therapy in Patients With Persistent Requirement for Vasopressor Support After 96-Hour Infusion With Commercial Drotrecogin Alfa (Activated).
• Date of first enrolment: 13/08/2004
• Target sample size: 270
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-001319-71
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Afghanistan, Spain, United States

Contacts

• Name: Clinical Operations
• Affiliation: Lilly S.A.

• Name: Clinical Operations
• Affiliation: Lilly S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
[1] Are adult (?18 year old) with severe sepsis that have been treated with
at least 84 hours of a planned 96-hour infusion of commercial
drotrecogin alfa (activated) under the applicable label in the
investigative site country.
[2] Continues to require vasopressor support (epinephrine, phenylephrine,
vasopressin, or norepinephrine) at any dose or dopamine ?5?g/kg/min
at the completion of at least 84 hours of a planned 96-hour infusion of
therapy with commercial drotrecogin alfa (activated).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 135
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 135

Exclusion criteria:
[3] Expected to require extensive and/or multiple surgical procedure(s)
(i.e. staging surgery for burn patients) within the next 3 days.
[4] Patients with a platelet count <30,000/mm3.
[5] Are receiving therapeutic heparin, defined as ?15,000 IU per day.
Unfractionated heparin up to 15 U/kg/hr may be used in conjunction
with acute hemodialysis or continuous renal replacement therapy.
[6] Are not expected to survive the 24 day (maximum) Study Treatment
and Post Study Treatment Period given their preexisting uncorrectable
medical condition.
[7] Are moribund and death is perceived to be imminent within 24 hours.
[8] Patients whose family and/or primary physician have not committed to
aggressive management of the patient. For instance patients or
patients? authorized representative is unwilling to allow red blood cell
transfusions or an advanced directive to withhold life-sustaining
treatment, with the exception of cardiopulmonary resuscitation (CPR),
is present.
[9] Have received treatment within the last 30 days with a drug that has
not received regulatory approval for any indication at the time of study
entry.
[10] Are pregnant or are lactating and the milk is to be ingested by the
child.
[11] Are contraindicated for treatment with drotrecogin alfa (activated)
under the applicable label in the investigative site country.
[12] Have no completed written informed consent signed by the patient or
the patient?s legal representative.
[13] No longer dependent upon vasopressors


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

in severe sepsis patients with persistent vasopressordependent hypotension

Intervention(s)

Product Name: XIGRIS
Product Code: LY203638
Pharmaceutical Form: Powder for injection
INN or Proposed INN: Drotrecogina Alfa Activada
CAS Number: 98530-76-8
Current Sponsor code: Xigris
Other descriptive name: LY203638
Concentration unit: µg/kg microgram(s)/kilogram
Concentration type: equal
Concentration number: 24-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: later than 72 hours after initiation of the study drug

Main Objective: To investigate, in severe sepsis patients with persistent vasopressordependent
hypotension at the end of a 96-hour infusion of commercial
drotrecogin alfa (activated), whether continued administration of
drotrecogin alfa (activated) for up to 72 additional hours results in
more rapid resolution of vasopressor-dependent hypotension versus
placebo.

Primary end point(s): The primary efficacy measurement will be time to resolution of vasopressor-dependent hypotension.

Secondary Objective: To evaluate if extended treatment with drotrecogin alfa (activated)
compared with placebo reduces 28-day* all cause mortality (i.e.,
mortality assessed 28-days from the start of commercial drug therapy)
and in hospital mortality.
? To evaluate the effects of extended administration of drotrecogin alfa
(activated) compared with placebo on cardiovascular, hematology,
hepatic, renal, and respiratory function as assessed by available
laboratory and physiologic parameters over the 14-day interval from
the start of commercial drug therapy.
? To evaluate the effects of extended administration of drotrecogin alfa
(activated) compared with placebo on the concentrations of various
biomarkers (e.g., Protein C, D-Dimer, Prothrombin Time) at the start
and stop of the extended infusion.
? To investigate the safety profile (e.g. study drug related bleeding
events) of an extended infusion of drotrecogin alfa (activated) over a
24-day study.

Secondary Outcome(s)

Secondary end point(s): Secondary efficacy measurements will be obtained by comparing organ function
(assessed by SOFA, including cardiovascular SOFA) between patients administered
drotrecogin alfa (activated) or placebo for the extended infusion period and retrospective
to 1 day prior to the initiation of commercial drotrecogin alfa (activated). This
assessment will be done each day the patient is receiving study drug, in the ICU and
hospitalized in the study hospital (up to and including Study Day 14).
Biomarker evaluation. All patients will have central laboratory specimens drawn for
specific biomarker assessment at the start and end of the study drug infusion. These
biomarkers will include D-dimer, Protein C levels and Prothrombin Time.
28-day all cause mortality and in-hospital mortality. All patients will be classified at
Day 28 as either ?alive? or ?dead.? Patients who are discharged from the study hospital
before Day 28 will be contacted to determine their survival status. For example, a patient
who is discharged from the study hospital on Study Day 16 and dies while at home on
Study Day 20 will be classified as ?dead.? Patients who die while hospitalized in the
study hospital will be classified as ?dead.? Patients who are still hospitalized after Study
Day 28 will be followed up through hospital discharge or a maximum of 90 days,
whichever comes first, to assess in-hospital mortality.

Timepoint(s) of evaluation of this end point: 90 days

Secondary ID(s)

F1K-MC-EVBQ

Source(s) of Monetary Support

Lilly S.A.

Ethics review

Status: Approved
Approval date: 26/04/2004
Contact:

Results

• Results available: Yes
• Date Posted: 03/01/2017
• Date Completed: 08/05/2007
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2004-001319-71/results