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

NCT ID: NCT01420744

Last Updated: 2015-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2015-04-30

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.

Conditions

Community Acquired Pneumonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

BT086 infusion

Group Type: EXPERIMENTAL

BT086

Intervention Type: DRUG

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.

1% Human Albumin infusion

Group Type: PLACEBO_COMPARATOR

1% Human Albumin infusion

Intervention Type: DRUG

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)

Interventions

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.

Intervention Type: 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)

Intervention Type: DRUG

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Biotest

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tobias Welte, MD

Role: PRINCIPAL_INVESTIGATOR

Hannover Medical School

Locations

401

Brussels, , Belgium

108

Berlin, , Germany

114

Chemnitz, , Germany

118

Cologne, , Germany

119

Cologne, , Germany

110

Dresden, , Germany

111

Erfurt, , Germany

116

Frankfurt, , Germany

117

Greifswald, , Germany

103

Halle, , Germany

115

Hamburg, , Germany

101

Hanover, , Germany

107

Homburg/Saar, , Germany

109

Lübeck, , Germany

106

Marburg, , Germany

120

Stuttgart, , Germany

105

Tübingen, , Germany

113

Wuppertal, , Germany

213

Badalona, , Spain

201

Barcelona, , Spain

206

Barcelona, , Spain

204

Girona, , Spain

207

Madrid, , Spain

208

Mataró, , Spain

210

Palma de Mallorca, , Spain

212

Sabadell, , Spain

209

Santiago de Compostela, , Spain

205

Tarragona, , Spain

211

Terrassa, , Spain

203

Valencia, , Spain

303

Cardiff, , United Kingdom

304

Kings Lynn, Norfolk, , United Kingdom

301

London, , United Kingdom

306

London, , United Kingdom

302

Poole, Dorset, , United Kingdom

305

Reading, Berkshire, , United Kingdom

Countries

Belgium; Germany; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33351126 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29632995 (View on PubMed)

Other Identifiers

CIGMA Study 982

Identifier Type: -

Identifier Source: org_study_id