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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Biotest
Sponsor:
Information provided by (Responsible Party):
Biotest
ClinicalTrials.gov Identifier:
NCT01420744
First received: August 19, 2011
Last updated: March 7, 2014
Last verified: May 2013
  Purpose

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).


Condition Intervention Phase
Community Acquired Pneumonia
Drug: BT086
Drug: 1% Human Albumin infusion
Phase 2

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by Biotest:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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).


Estimated Enrollment: 160
Study Start Date: August 2011
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BT086 infusion 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 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.

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)


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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01420744

Contacts
Contact: Andrea Wartenberg-Demand, MD ++49 6103 801 ext 497 wartenberg-demand@biotest.de
Contact: Iris Bobenhausen, PhD ++49 6103 801 ext 2124 iris_bobenhausen@biotest.de

Locations
Belgium
401 Not yet recruiting
Brussels, Belgium
Germany
108 Recruiting
Berlin, Germany
114 Recruiting
Chemnitz, Germany
110 Recruiting
Dresden, Germany
111 Recruiting
Erfurt, Germany
116 Recruiting
Frankfurt, Germany
117 Recruiting
Greifswald, Germany
103 Recruiting
Halle, Germany
115 Recruiting
Hamburg, Germany
101 Recruiting
Hannover, Germany
107 Recruiting
Homburg/Saar, Germany
119 Not yet recruiting
Köln, Germany
118 Recruiting
Köln, Germany
109 Recruiting
Lübeck, Germany
106 Recruiting
Marburg, Germany
120 Recruiting
Stuttgart, Germany
105 Recruiting
Tübingen, Germany
113 Recruiting
Wuppertal, Germany
Spain
213 Recruiting
Badalona, Spain
201 Recruiting
Barcelona, Spain
206 Recruiting
Barcelona, Spain
204 Recruiting
Girona, Spain
207 Recruiting
Madrid, Spain
208 Recruiting
Mataro, Spain
210 Recruiting
Palma de Mallorca, Spain
212 Recruiting
Sabadell, Spain
209 Recruiting
Santiago de Compostela, Spain
205 Recruiting
Tarragona, Spain
211 Recruiting
Terrassa, Spain
203 Recruiting
Valencia, Spain
United Kingdom
303 Not yet recruiting
Cardiff, United Kingdom
304 Not yet recruiting
Kings Lynn, Norfolk, United Kingdom
306 Not yet recruiting
London, United Kingdom
301 Not yet recruiting
London, United Kingdom
302 Not yet recruiting
Poole, Dorset, United Kingdom
305 Not yet recruiting
Reading, Berkshire, United Kingdom
Sponsors and Collaborators
Biotest
Investigators
Principal Investigator: Tobias Welte, MD Hannover Medical School
  More Information

No publications provided

Responsible Party: Biotest
ClinicalTrials.gov Identifier: NCT01420744     History of Changes
Other Study ID Numbers: CIGMA Study 982
Study First Received: August 19, 2011
Last Updated: March 7, 2014
Health Authority: Germany: Paul-Ehrlich-Institut
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Belgium: Federal Agency for Medicines and Health Products, FAMHP
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Biotest:
Endotracheal ventilation
Bacterial pneumonia

Additional relevant MeSH terms:
Pneumonia
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Albunex
Contrast Media
Diagnostic Uses of Chemicals
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 21, 2014