Status Acronym ISRCTN EudraCT NCT (clinicaltrials.gov) DRKS
Active 982 2010-022380-35 NCT01420744

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)

Purpose / Objectives

Primary Outcome

  • Ventilator Free Days
    VFDs are defined as the number of days between successful weaning from endotracheal ventilation and day 28 after study enrolment.

    • The primary endpoint is the increase of ventilator free days measured in sCAP patients treated with adjunctive BT086 and the appropriate standard of care treatment compared to patients treated with placebo and the appropriate standard of care

Secondary Outcomes

  • 28-day all cause mortality [ Time Frame: 28 days (672 hours from randomization) ]
    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) ]
    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 ]
    The date and time of admission to and discharge from the ICU will be recorded in the 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 ]
    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 ]
    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 ]

    Vasopressor-free days will be calculated in a similar manner to VFDs, as described above. Vasopressors include doputamine, epinephrine, dopamine, and norepinephrine.

    A day is considered as a vasopressor-free day if a patient does not receive

    • Doputamine >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.

Diagnosis

  • Bacterial Pneumonia
  • Pneumonie (ambulant erworben) (English name missing)

Target population

Age

18-99

Inclusion criteria

  • Written informed consent:

    • given by the patient or
    • a legal/authorised representative of the patient or
    • a waiver for written informed consent due to emergency situation, in compliance with all local legal requirements.
  • Male or female patients aged 18 years or older
  • Patient receiving adequate antibiotic treatment for pneumonia

  • Prior to endotracheal ventilation and therapy, the patient must have at least one of the following two signs of inflammation:

    • Fever/Hypothermia Fever defined as an oral temperature of >38°C, tympanic temperature of >38°C or rectal temperature of >38.5°C, or hypothermia (rectal temperature <35.5°C) or
    • White blood cell (WBC) count >10,000/mm³ or WBC <4,500/mm³

  • Patient must have at least one of the following signs and symptoms of pneumonia:

    • New or increased cough
    • Production of purulent sputum or change in sputum characteristics
    • Dyspnoea or tachypnoea (respiratory rate >20 breaths/minute)
    • Pleuritic chest pain
    • Auscultatory findings on pulmonary examination of rales and/or crackles and/or evidence of pulmonary consolidation (e.g. dullness on percussion, bronchial breath sounds, or egophony)
  • Radiological (or other imaging technique) evidence of (an) infiltrate(s) consistent with bacterial pneumonia
  • Pneumonia has been acquired outside the hospital. In hospital-admitted patients, pneumonia has been diagnosed a maximum of 72 hours after admission. Patients from nursing homes or similar institutions are eligible.
  • Major sCAP criterion: need for endotracheal ventilation
  • Treatment of patient with BT086 must start within 12 hours but not earlier than 1 hour after start of endotracheal ventilation

Exclusion criteria

  • For incapacitated patients: any indication that the patient's presumed will would be against inclusion in the trial
  • Patients with suspected hospital-acquired pneumonia
  • Severe lung diseases interfering with sCAP therapy e.g. patients with cystic fibrosis,
  • Patients receiving Xigris® (drotrecogin alfa, activated Protein C) or medications not approved for sCAP (e.g. Dornase alpha) are excluded from inclusion in the study
  • Patients on dialysis
  • Presence of other severe diseases impairing life expectancy (e.g. patients are not expected to survive 28 days given their pre-existing uncorrectable medical condition).
  • Patients unable to be treated due to obesity
  • Selective, absolute IgA deficiency with known antibodies to IgA
  • Patients with neutrophil count <1,000/mm³ or platelet count <50,000/mm³
  • Pregnant or lactating women. A pregnancy test will be performed in all women aged <65 years and the result must be available at study inclusion.
  • Known relevant intolerance to immunoglobulins, vaccines or other substances of human origin
  • Participation in another interventional clinical trial within 30 days before entering the study or during the study, and/or previous participation in this study (participation in non-interventional trials is allowed).

Study design

  • Phase II
  • Multicenter
  • Double-blind
  • Randomized
  • Placebo-controlled

Intervention

  • Drug: BT086

    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 IgM content of BT086 which is 23%.

    Infusion rate:

    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.

  • 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)

Documents (password protected)

Go to download area (no documents yet)

Networks

Responsibilities in overall study

Sponsor

Biotest AG

Sponsor representative

Andreas Spiller

Prof. Dr. med. Tobias Welte

(National) Coordinating Investigator

Prof. Dr. med. Tobias Welte