Clinical trial NCT01420744: Safety and Efficacy Study of BT086 to Evaluate Adjunctive Therapy in sCAP
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Community Acquired Pneumonia
Keywords: Endotracheal ventilation
Bacterial pneumonia
Lead sponsor: Biotest
Sponsor class: INDUSTRY
First posted: 2011-08-22
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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, tympanic, oesophageal or vesical temperature of \>38°C, tympanic temperature of \>38°C or rectal temperature of \>38.5°C, or hypothermia (rectal temperature \<35.5°C) (measurement with temperature probe or device) 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).

Primary outcomes:
measure: Ventilator Free Days (VFDs)
timeFrame: 28 days
Secondary outcomes:
measure: 28-day all cause mortality
timeFrame: 28 days (672 hours from randomization)
measure: 28-day pneumonia-cause mortality
timeFrame: 28 days (672 hours from randomization)
measure: Time (days) to discharge from ICU
timeFrame: 28 days
measure: Time (days) to discharge from hospital
timeFrame: 28 days
measure: SOFA: Score Sequential Organ Failure Assessment
timeFrame: 28 days
measure: Vasopressor-free days
timeFrame: 28 days
measure: Glasgow Coma Score
timeFrame: 28 days
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: 401
city: Berlin
country: Germany
facility: 108
city: Chemnitz
country: Germany
facility: 114
city: Dresden
country: Germany
facility: 110
city: Erfurt
country: Germany
facility: 111
city: Frankfurt
country: Germany
facility: 116
city: Greifswald
country: Germany
facility: 117
city: Halle
country: Germany
facility: 103
city: Hamburg
country: Germany
facility: 115
city: Hannover
country: Germany
facility: 101
city: Homburg/Saar
country: Germany
facility: 107
city: Köln
country: Germany
facility: 118
city: Köln
country: Germany
facility: 119
city: Lübeck
country: Germany
facility: 109
city: Marburg
country: Germany
facility: 106
city: Stuttgart
country: Germany
facility: 120
city: Tübingen
country: Germany
facility: 105
city: Wuppertal
country: Germany
facility: 113
city: Badalona
country: Spain
facility: 213
city: Barcelona
country: Spain
facility: 201
city: Barcelona
country: Spain
facility: 206
city: Girona
country: Spain
facility: 204
city: Madrid
country: Spain
facility: 207
city: Mataro
country: Spain
facility: 208
city: Palma de Mallorca
country: Spain
facility: 210
city: Sabadell
country: Spain
facility: 212
city: Santiago de Compostela
country: Spain
facility: 209
city: Tarragona
country: Spain
facility: 205
city: Terrassa
country: Spain
facility: 211
city: Valencia
country: Spain
facility: 203
city: Cardiff
country: United Kingdom
facility: 303
city: Kings Lynn, Norfolk
country: United Kingdom
facility: 304
city: London
country: United Kingdom
facility: 301
city: London
country: United Kingdom
facility: 306
city: Poole, Dorset
country: United Kingdom
facility: 302
city: Reading, Berkshire
country: United Kingdom
facility: 305
Study officials:
affiliation: Hannover Medical School
name: Tobias Welte, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jahn K, Handtke S, Palankar R, Weissmuller S, Nouailles G, Kohler TP, Wesche J, Rohde M, Heinz C, Aschenbrenner AF, Wolff M, Schuttrumpf J, Witzenrath M, Hammerschmidt S, Greinacher A. Pneumolysin induces platelet destruction, not platelet activation, which can be prevented by immunoglobulin preparations in vitro. Blood Adv. 2020 Dec 22;4(24):6315-6326. doi: 10.1182/bloodadvances.2020002372.
citation: Welte T, Dellinger RP, Ebelt H, Ferrer M, Opal SM, Singer M, Vincent JL, Werdan K, Martin-Loeches I, Almirall J, Artigas A, Ignacio Ayestaran J, Nuding S, Ferrer R, Sirgo Rodriguez G, Shankar-Hari M, Alvarez-Lerma F, Riessen R, Sirvent JM, Kluge S, Zacharowski K, Bonastre Mora J, Lapp H, Wobker G, Achtzehn U, Brealey D, Kempa A, Sanchez Garcia M, Brederlau J, Kochanek M, Reschreiter HP, Wise MP, Belohradsky BH, Bobenhausen I, Dalken B, Dubovy P, Langohr P, Mayer M, Schuttrumpf J, Wartenberg-Demand A, Wippermann U, Wolf D, Torres A. Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study). Intensive Care Med. 2018 Apr;44(4):438-448. doi: 10.1007/s00134-018-5143-7. Epub 2018 Apr 9.