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Safety and Efficacy Study of BT086 to Evaluate Adjunctive Therapy in sCAP (CIGMA)

Primary Purpose

Community Acquired Pneumonia

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
BT086
1% Human Albumin infusion
Sponsored by
Biotest
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Community Acquired Pneumonia focused on measuring Endotracheal ventilation, Bacterial pneumonia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • 401
  • 108
  • 114
  • 110
  • 111
  • 116
  • 117
  • 103
  • 115
  • 101
  • 107
  • 118
  • 119
  • 109
  • 106
  • 120
  • 105
  • 113
  • 213
  • 201
  • 206
  • 204
  • 207
  • 208
  • 210
  • 212
  • 209
  • 205
  • 211
  • 203
  • 303
  • 304
  • 301
  • 306
  • 302
  • 305

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

BT086 infusion

1% Human Albumin infusion

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

28-day all cause mortality
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
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
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
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
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
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
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).

Full Information

First Posted
August 19, 2011
Last Updated
July 28, 2015
Sponsor
Biotest
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1. Study Identification

Unique Protocol Identification Number
NCT01420744
Brief Title
Safety and Efficacy Study of BT086 to Evaluate Adjunctive Therapy in sCAP
Acronym
CIGMA
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

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biotest

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Community Acquired Pneumonia
Keywords
Endotracheal ventilation, Bacterial pneumonia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
160 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BT086 infusion
Arm Type
Experimental
Arm Title
1% Human Albumin infusion
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
BT086
Intervention Description
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%. 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.
Intervention Type
Drug
Intervention Name(s)
1% Human Albumin infusion
Intervention Description
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)
Primary Outcome Measure Information:
Title
Ventilator Free Days (VFDs)
Description
VFDs are defined as the number of days between successful weaning from endotracheal ventilation and day 28 after study enrolment.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
28-day all cause mortality
Description
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.
Time Frame
28 days (672 hours from randomization)
Title
28-day pneumonia-cause mortality
Description
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 Frame
28 days (672 hours from randomization)
Title
Time (days) to discharge from ICU
Description
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 Frame
28 days
Title
Time (days) to discharge from hospital
Description
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.
Time Frame
28 days
Title
SOFA: Score Sequential Organ Failure Assessment
Description
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.
Time Frame
28 days
Title
Vasopressor-free days
Description
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.
Time Frame
28 days
Title
Glasgow Coma Score
Description
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).
Time Frame
28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tobias Welte, MD
Organizational Affiliation
Hannover Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
401
City
Brussels
Country
Belgium
Facility Name
108
City
Berlin
Country
Germany
Facility Name
114
City
Chemnitz
Country
Germany
Facility Name
110
City
Dresden
Country
Germany
Facility Name
111
City
Erfurt
Country
Germany
Facility Name
116
City
Frankfurt
Country
Germany
Facility Name
117
City
Greifswald
Country
Germany
Facility Name
103
City
Halle
Country
Germany
Facility Name
115
City
Hamburg
Country
Germany
Facility Name
101
City
Hannover
Country
Germany
Facility Name
107
City
Homburg/Saar
Country
Germany
Facility Name
118
City
Köln
Country
Germany
Facility Name
119
City
Köln
Country
Germany
Facility Name
109
City
Lübeck
Country
Germany
Facility Name
106
City
Marburg
Country
Germany
Facility Name
120
City
Stuttgart
Country
Germany
Facility Name
105
City
Tübingen
Country
Germany
Facility Name
113
City
Wuppertal
Country
Germany
Facility Name
213
City
Badalona
Country
Spain
Facility Name
201
City
Barcelona
Country
Spain
Facility Name
206
City
Barcelona
Country
Spain
Facility Name
204
City
Girona
Country
Spain
Facility Name
207
City
Madrid
Country
Spain
Facility Name
208
City
Mataro
Country
Spain
Facility Name
210
City
Palma de Mallorca
Country
Spain
Facility Name
212
City
Sabadell
Country
Spain
Facility Name
209
City
Santiago de Compostela
Country
Spain
Facility Name
205
City
Tarragona
Country
Spain
Facility Name
211
City
Terrassa
Country
Spain
Facility Name
203
City
Valencia
Country
Spain
Facility Name
303
City
Cardiff
Country
United Kingdom
Facility Name
304
City
Kings Lynn, Norfolk
Country
United Kingdom
Facility Name
301
City
London
Country
United Kingdom
Facility Name
306
City
London
Country
United Kingdom
Facility Name
302
City
Poole, Dorset
Country
United Kingdom
Facility Name
305
City
Reading, Berkshire
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
33351126
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.
Results Reference
derived
PubMed Identifier
29632995
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.
Results Reference
derived

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Safety and Efficacy Study of BT086 to Evaluate Adjunctive Therapy in sCAP

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