A Phase 2 Study to Evaluate Dose and Duration of Treatment of Drotrecogin Alfa (Activated) Using Serial Measurements of Protein C in Patients with Severe Sepsis and Multiple Organ Dysfunction - RESPOND

Phase 1

• Conditions: severe sepsis; MedDRA version: 8.1 Level: LLT Classification code 10040047 Term: Sepsis

• Registration Number: EUCTR2006-002112-99-GB
• Lead Sponsor: Eli Lilly & Company Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2008-02-21
• Study Completion: 2009-08-29
• Last Update Posted: 25 November 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 488

Inclusion Criteria

Adult patients (>=18 years old) with severe sepsis and multiple organ dysfunction
Patients with severe sepsis are defined by the following criteria. Both criteria must be met for a diagnosis of severe sepsis with multiple organ dysfunction.
Presence of a suspected or proven infection. Patients with a suspected infection must have evidence of an infection, such as white blood cells in a normally sterile body fluid, perforated viscus, chest x-ray consistent with pneumonia and associated with purulent sputum production, or a clinical syndrome associated with a high probability of infection, for example, purpura fulminans or ascending cholangitis.
Presence of multiple organ dysfunction, which is defined as two or more sepsis-associated organ dysfunctions defined below.
Note: A patient must have organ dysfunctions attributable to the sepsis episode. The organ dysfunctions must be newly developed and not explained by underlying disease processes or by the effects of concomitant therapy. A non-sepsis-induced organ dysfunction may not be used to qualify the patient for the study even if the organ dysfunction worsens as a result of the sepsis episode.
Cardiovascular: An arterial systolic blood pressure (SBP) of <=90 mm Hg or a mean arterial pressure (MAP) <=70 mm Hg for at least 1 hour despite adequate fluid resuscitation, adequate intravascular volume status, or the need for vasopressors to maintain SBP >=90 mm Hg or MAP >=70 mm Hg.
Adequate fluid resuscitation or adequate intravascular volume is defined as one or more of the following: (a) the administration of an intravenous fluid bolus (>=500 mL of crystalloid solution, >=20 g of albumin, or >=200 mL of other colloid administered over 30 minutes or less); (b) pulmonary arterial wedge pressure >=12 mm Hg; or (c) central venous pressure >=8 mm Hg.
Vasopressors are defined as the following: (a) dopamine >=5 g/kg/min or (b) norepinephrine, epinephrine, phenylephrine, or vasopressin at any dose. Dobutamine or dopexamine are not considered vasopressors.
Renal: Average output <0.5 mL/kg/h for 1 hour despite adequate fluid resuscitation (defined above).
In the presence of preexisting impairment of renal function (defined as a serum creatine concentration >2 times the upper limit of the normal reference range for the institution prior to the onset of sepsis), the patient must meet two of the other four organ dysfunction criteria.
Respiratory: Evidence of acute pulmonary dysfunction: PaO2/FiO2 <=250 (adjusted for altitude) and, if measured, a pulmonary capillary wedge pressure not suggestive of central volume overload. If the lung is also the suspected site of infection, the patient must have a PaO2/FiO2 <200.
Hematology: Platelet count <80,000/mm3 or a 50% decrease in platelet count from the highest value recorded over the 3 days prior to study entry.
Unexplained metabolic acidosis: Defined by (1) pH <=7.30 or base deficit >=5.0 mEq/L AND (2) a plasma lactate level >1.5 times the upper limit of normal for the reporting laboratory.

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
F.1.3 Elderly (>=65 years) y

Exclusion Criteria

Have documented multiple organ dysfunction for greater than 24 hours prior to the start of study drug or the first documented sepsis-induced organ dysfunction occurred greater than 36 hours prior to the start of study drug.
Weigh less than 30 kg or greater than 135 kg.
Have a platelet count <30,000/mm3.
Patients with active internal bleeding or at increased risk for bleeding, for example:
Any major surgery, defined as surgery that requires general or spinal anesthesia, performed within the 12-hour period immediately preceding the drotrecogin alfa (activated) infusion, or any postoperative patient who demonstrates evidence of active bleeding, or any patient with planned or anticipated surgery during the infusion period (for example, patients with staged surgeries or burn patients with planned excisions and grafting during the infusion period). (Note: Peritoneal lavage alone is not considered planned surgery.)
Biopsy or surgical procedure of a closed-space within the 12 hours immediately preceding the drotrecogin alfa (activated) infusion where there is a high risk of significant bleeding and where it would not be possible to control bleeding by external pressure.
History (within the previous 3 months) of stroke or severe head trauma that required hospitalization or intracranial surgery.
History of intracranial arteriovenous malformation, cerebral aneurysm, or central nervous system mass lesion.
Patients with an epidural catheter or who are anticipated to receive an epidural catheter during drotrecogin alfa (activated) infusion.
History of congenital bleeding diatheses (for example, hemophilia).
Gastrointestinal bleeding within the 6 weeks prior to study entry that required medical intervention unless definitive endoscopic procedure or surgery has been performed.
Trauma patients at increased risk of bleeding (for example, flail chest; significant contusion to lung, liver, or spleen; retroperitoneal bleed; pelvic fracture; compartment syndrome).
Patients with known esophageal varices, chronic jaundice, cirrhosis, or chronic ascites.
Have a concurrent need for any of the following medications during the drotrecogin alfa (activated) infusion:
Therapeutic heparin, defined as unfractionated heparin >15,000 units/day within 8 hours of study entry or low molecular weight heparin used at any dose higher or more frequent than the recommended dose in the product label for prophylaxis within 12 hours of study entry.
Warfarin, if used within 7 days of study entry or warfarin-type medications within <5 half-lives at the time of study entry and where the prothrombin time (PT) is prolonged beyond the upper limit of normal for the institution.
Antiplatelets such as ticlopidine, clopidogrel, or acetylsalicylic acid (ASA) >650 mg/day or compounds that contain ASA >650 mg/day within 3 days prior to study entry.
Thrombolytic therapy (unless used to treat an intra-catheter thrombosis; however, care should be taken to avoid systemic administration) if used within 3 days of study enrollment (for example, streptokinase, tPA, rPA, and urokinase).
Glycoprotein IIb/IIIa receptor antagonists within 7 days of study entry.
Antithrombin infusion of >10,

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified