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

• Sponsor: Biotest (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01420744
• Collaborator: (none)
• Enrollment: 160
• Locations: 36
• Arms: 2
• Duration (Months): 44
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.1

Study Details

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).

Condition or Disease	Intervention/Treatment	Phase
Community Acquired Pneumonia	Drug: BT086; Drug: 1% Human Albumin infusion	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, 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)
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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)

Outcome Measures

Primary Outcome Measures

1. Ventilator Free Days (VFDs) [28 days]

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

Secondary Outcome Measures

1. 28-day all cause mortality [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.

2. 28-day pneumonia-cause mortality [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".

3. Time (days) to discharge from ICU [28 days]

   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.

4. Time (days) to discharge from hospital [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.

5. SOFA: Score Sequential Organ Failure Assessment [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.

6. Vasopressor-free days [28 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.

7. Glasgow Coma Score [28 days]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	401	Brussels		Belgium
2	108	Berlin		Germany
3	114	Chemnitz		Germany
4	110	Dresden		Germany
5	111	Erfurt		Germany
6	116	Frankfurt		Germany
7	117	Greifswald		Germany
8	103	Halle		Germany
9	115	Hamburg		Germany
10	101	Hannover		Germany
11	107	Homburg/Saar		Germany
12	118	Köln		Germany
13	119	Köln		Germany
14	109	Lübeck		Germany
15	106	Marburg		Germany
16	120	Stuttgart		Germany
17	105	Tübingen		Germany
18	113	Wuppertal		Germany
19	213	Badalona		Spain
20	201	Barcelona		Spain
21	206	Barcelona		Spain
22	204	Girona		Spain
23	207	Madrid		Spain
24	208	Mataro		Spain
25	210	Palma de Mallorca		Spain
26	212	Sabadell		Spain
27	209	Santiago de Compostela		Spain
28	205	Tarragona		Spain
29	211	Terrassa		Spain
30	203	Valencia		Spain
31	303	Cardiff		United Kingdom
32	304	Kings Lynn, Norfolk		United Kingdom
33	301	London		United Kingdom
34	306	London		United Kingdom
35	302	Poole, Dorset		United Kingdom
36	305	Reading, Berkshire		United Kingdom

Sponsors and Collaborators

• Biotest

Investigators

• Principal Investigator: Tobias Welte, MD, Hannover Medical School

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Biotest
• ClinicalTrials.gov Identifier: NCT01420744
• Other Study ID Numbers: CIGMA Study 982
• First Posted: Aug 22, 2011
• Last Update Posted: Jul 29, 2015
• Last Verified: Jul 1, 2015

• Keywords provided by Biotest: Endotracheal ventilation; Bacterial pneumonia
• Additional relevant MeSH terms: Pneumonia

Study Results

No Results Posted as of Jul 29, 2015