Safety and Efficacy Study of BT086 to Evaluate Adjunctive Therapy in sCAP (CIGMA)
The purpose of this study is to determine whether the adjunctive therapy to standard antibiotic treatment of BT086 is safe and effective of decreasing the days patients require endotracheal ventilation due to Severe Community-Acquired Pneumonia (sCAP).
Community Acquired Pneumonia
Drug: 1% Human Albumin infusion
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel-group, Adaptive Group-sequential Phase II Study, to Determine the Efficacy and Safety of BT086 as an Adjunctive Treatment in Severe Community Acquired Pneumonia (sCAP)|
- Ventilator Free Days (VFDs) [ Time Frame: 28 days ] [ Designated as safety issue: No ]VFDs are defined as the number of days between successful weaning from endotracheal ventilation and day 28 after study enrolment.
- 28-day all cause mortality [ Time Frame: 28 days (672 hours from randomization) ] [ Designated as safety issue: No ]All patients will be classified as either "alive at Study Day 28" or, if dead, "dead at Study Day 28", regardless of cause of death.
- 28-day pneumonia-cause mortality [ Time Frame: 28 days (672 hours from randomization) ] [ Designated as safety issue: No ]All patients will be classified as either "alive at Study Day 28" or, if dead, "dead at Study Day 28, with pneumonia as cause of death".
- Time (days) to discharge from ICU [ Time Frame: 28 days ] [ Designated as safety issue: No ]The date and time of admission to and discharge from the ICU will be recorded in the Case Report Form (CRF). The time to discharge from the ICU will be calculated as the number of days spent in the ICU.
- Time (days) to discharge from hospital [ Time Frame: 28 days ] [ Designated as safety issue: No ]The date and time of admission to and discharge from the hospital will be recorded in the CRF. The time to discharge from the hospital will be calculated as the number of days spent in the hospital.
- SOFA: Score Sequential Organ Failure Assessment [ Time Frame: 28 days ] [ Designated as safety issue: No ]Each organ system (cardiovascular, haematology, hepatic, renal, respiratory) will be scored using the SOFA methodology.For analysis, a patient will receive a score on each day (Study Days 1-7, Day 14, Day 21, and Day 28). Mean changes in organ function scores over time and percentages of patients whose organ function has resolved will be compared between treatment groups.
- Vasopressor-free days [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Vasopressor-free days will be calculated in a similar manner to VFDs, as described above. Vasopressors include dobutamine, epinephrine, dopamine, and norepinephrine.
A day is considered as a vasopressor-free day if a patient does not receive
- Dobutamine >2.5 µg/kg/min or/and
- Epinephrine (adrenalin) >=2.5 µg/min or/and
- Dopamine >=2.5 µg/kg/min or/and
- Norepinephrine >=0.014 µg/kg/min for 4 hours per day.
- Glasgow Coma Score [ Time Frame: 28 days ] [ Designated as safety issue: No ]The Glasgow Coma Scale will be scored using the Glasgow Coma Score methodology. The patient will be assessed by calculating the score on each study day (Day -1 through to Day 28).
|Study Start Date:||August 2011|
|Estimated Study Completion Date:||March 2015|
|Estimated Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
|Experimental: BT086 infusion||
BT086 will be administered per intravenous infusion (IV). The dose to be administered is 3.65 mL /kg bw/day and is calculated by the mean Immunoglobulin M (IgM) content of BT086 which is 23%.
Starting rate is 0.1 mL/min. Maximum infusion rate is 0.5 mL/min (target infusion rate) Treatment will be administered over a 5-day period.
|Placebo Comparator: 1% Human Albumin infusion||
Drug: 1% Human Albumin infusion
1% Albumin will be administered per intravenous infusion (IV). The dose to be administered is 3.65 mL /kg bw/day.
Infusion rate:Starting rate is 0.1 mL/min. Maximum infusion rate is 0.5 mL/min (target infusion rate). Rate is to be raised in steps of 0.1 mL every 10 min until the target infusion rate is reached.
Treatment will be administered over a 5-day period.
Starting rate is 0.1 mL/min. Maximum infusion rate is 0.5 mL/min (target infusion rate)
Severe Community-Acquired Pneumonia (sCAP) is usually defined clinically as pneumonia acquired from outside the hospital (CAP) that requires intensive medical care. Mortality of (s)CAP patients admitted to ICU range from 35-58% depending on time and admission of the patient and has not much improved in the last years.
BT086 contains a sufficient number of antibodies against the most frequent pathogens as well as antibodies against lipopolysaccharides and lipid A. Therefore, it can be assumed that administration of BT086 early in the clinical course of a severe infection such as sCAP may provide an effective adjunctive treatment to standard antibiotic therapy for sCAP patients.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01420744
|Palma de Mallorca, Spain|
|Santiago de Compostela, Spain|
|Cardiff, United Kingdom|
|Kings Lynn, Norfolk, United Kingdom|
|London, United Kingdom|
|London, United Kingdom|
|Poole, Dorset, United Kingdom|
|Reading, Berkshire, United Kingdom|
|Principal Investigator:||Tobias Welte, MD||Hannover Medical School|