Study to Demonstrate That Antibiotics Are Not Needed in Moderate Acute Exacerbations of COPD

NCT ID: NCT01892488

Last Updated: 2020-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 295 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-07
• Study Completion Date: 2019-06-05

Brief Summary

The ultimate goal is to reduce unnecessary antibiotic prescriptions which drive the development of antibiotic resistance in the community. The primary objective of ABACOPD is to demonstrate in a sufficiently sized clinical study that there is no relevant increase in the "failure-rate" for patients with acute moderate exacerbations of COPD (AE-COPD) treated with placebo instead of antibiotic treatment both on top of standard of care. A patient is classified as treatment failure if additional antibiotic therapy is required during treatment period or until the test of cure visit (TOC at day 30, primary endpoint).

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Study Design

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

Study Groups

lactose pill

Placebo for 5 days as supplement to standard of care for patients with AE-COPD

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Standard of care: Each patient will receive inhaled fast-acting bronchodilators (up to a maximum of 4 - 6 times daily 2 puffs (100µg) of salbutamol or other equivalent inhaled fast-acting bronchodilators), systemic corticosteroids (prednisolone 40mg/d p.o. for 7 - 10 days) and oxygen in case of hypoxemia in a standardized fashion. The pre-existing COPD medication will be continued as indicated.

Control intervention:

Placebo for 5 days as supplement to standard of care for patients with AE-COPD

Sultamicillin

Antibiotic therapy with aminopenicillin + betalactamase inhibitor (oral Sultamicillin (2 x 750mg)) for 5 days as supplement to standard of care for patients with AE-COPD

Group Type: EXPERIMENTAL

Sultamicillin

Intervention Type: DRUG

Standard of care: Each patient will receive inhaled fast-acting bronchodilators (up to a maximum of 4 - 6 times daily 2 puffs (100µg) of salbutamol or other equivalent inhaled fast-acting bronchodilators), systemic corticosteroids (prednisolone 40mg/d p.o. for 7 - 10 days) and oxygen in case of hypoxemia in a standardized fashion. The pre-existing COPD medication will be continued as indicated.

Experimental intervention:

Antibiotic therapy with aminopenicillin + betalactamase inhibitor (oral Sultamicillin (2 x 750mg)) for 5 days as supplement to standard of care for patients with AE-COPD.

Interventions

Sultamicillin

Standard of care: Each patient will receive inhaled fast-acting bronchodilators (up to a maximum of 4 - 6 times daily 2 puffs (100µg) of salbutamol or other equivalent inhaled fast-acting bronchodilators), systemic corticosteroids (prednisolone 40mg/d p.o. for 7 - 10 days) and oxygen in case of hypoxemia in a standardized fashion. The pre-existing COPD medication will be continued as indicated.

Experimental intervention:

Antibiotic therapy with aminopenicillin + betalactamase inhibitor (oral Sultamicillin (2 x 750mg)) for 5 days as supplement to standard of care for patients with AE-COPD.

Intervention Type: DRUG

Placebo

Standard of care: Each patient will receive inhaled fast-acting bronchodilators (up to a maximum of 4 - 6 times daily 2 puffs (100µg) of salbutamol or other equivalent inhaled fast-acting bronchodilators), systemic corticosteroids (prednisolone 40mg/d p.o. for 7 - 10 days) and oxygen in case of hypoxemia in a standardized fashion. The pre-existing COPD medication will be continued as indicated.

Control intervention:

Placebo for 5 days as supplement to standard of care for patients with AE-COPD

Intervention Type: DRUG

Other Intervention Names

aminopenicillin + betalactamase inhibitor; Placebo: Lactose pill

Eligibility Criteria

Inclusion Criteria

• Adults, either sex, older or equal than 40 years of age
• For female patients, the following conditions are to be met:

• has been postmenopausal for at least 1 year, or
• is surgically incapable of bearing children, or
• is of childbearing potential, and the following conditions are met:

• has a negative pregnancy test (urine- or serum-based) immediately before study entry (i.e., before the start of treatment or any other study procedure that could potentially harm the fetus), and one or more of following criteria
• must agree to abstinence or use an accepted method of contraception. The subject must agree to continue with the same method throughout the study.
• having only female sexual partners
• sexual relationship with sterile male partners only
• Patients diagnosed with COPD stages I-IV as defined by the Global initiative for chronic Obstructive Lung disease (GOLD).

and

• Doctor's diagnosis of acute (onset < 7 days) moderate exacerbation of COPD defined by a sustained worsening of the patient's condition (including at least 2 of the following symptoms: increased dyspnea, increased sputum production, sputum purulence and increased cough), from the stable state and beyond normal day-to-day variations, necessitating a change in regular medication in patient with underlying COPD, needing additional medical assistance.
• Absence of community acquired pneumonia or lower respiratory tract infection with a clear indication for antibiotic treatment as determined by Procalcitonin level < 0.25 ng/mL and/or absence of pulmonary infiltrates on routine chest x-ray.
• Smoking history of at least 10 Pack Years or more.
• Patients must be able to complete diaries and quality of life questionnaires.
• Patients must sign and date an informed consent prior to any study procedures.

Exclusion Criteria

• Severe exacerbation: defined by need for ventilatory support (indicated by severe dyspnea with failure to respond to emergency treatment and/or persistent hypoxemia (PaO2 <50 mm Hg despite O2 administration and / or respiratory acidosis (pH <7.35 and PaCO2> 45mmHg)) or mental confusion or circulatory insufficiency (need of vasopressors)
• Fever (>38.5°C)
• Known impaired hepatic or renal function
• Active or suspected tuberculosis infection of the respiratory tract
• Acute exacerbation of asthma
• Suspected or known hypersensitivity to, or suspected serious adverse reaction to sultamicillin; suspected or known hypersensitivity to penicillins or cephalosporins
• Immunosuppression or Immunosuppressive therapy (cytostatic chemotherapy within last 28 days or neutropenia (neutrophils < 1000/µ)l; systemic corticosteroids (≥20 mg prednisolon equivalent/day > 14 days; HIV-infection; immunosuppression after organ- or bone marrow transplant)- Patients with metastatic or hematological malignancy, splenectomized patients or patients with known hyposplenia or asplenia
• Oral/parenteral antibiotic use within 30 days prior to randomization (a singular administration of antibiotics prior to randomization is allowed)
• In-patient treatment within the last 30 days
• An antibiotic is clearly indicated for treatment of a known infection
• Known MRSA (methicillin-resistant Staphylococcus aureus) colonization or infection
• Patients with known bronchiectasis
• Patients with known bacterial airway colonization (>3 positive sputum cultures in the previous year)
• Progressively fatal disease, or life expectancy ≤6 months
• Mononucleosis
• Lymphatic leukemia
• Severe gastro-intestinal disorders with vomiting and diarrhea
• Women who are breast feeding
• Patients who have received treatment with any other investigational drug within 1 month prior to study entry, or have such treatment planned for the study period during treatment and follow up phase.
• Patients with mental conditions rendering them unable to understand the nature, scope, and possible consequences of the study.
• Patients unlikely to comply with the protocol, e.g., uncooperative attitude, inability to return for follow up visits, and unlikelihood of completing the study.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CAPNETZ Stiftung

OTHER

Sponsor Role: collaborator

Hannover Medical School

OTHER

Sponsor Role: lead

Responsible Party

Tobias Welte

Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gernot Rohde, Prof. Dr.

Role: STUDY_DIRECTOR

CAPNETZ Stiftung

Tobias Welte, Prof.Dr.

Role: PRINCIPAL_INVESTIGATOR

Hannover Medical School

Locations

Universitätsklinikum Aachen

Aachen, , Germany

Krankenhaus Bad Arolsen

Bad Arolsen, , Germany

Lungenklinik Ballenstedt

Ballenstedt, , Germany

Charité - Universitätsmedizin Berlin

Berlin, , Germany

HELIOS Klinikum Emil von Behring Berlin

Berlin, , Germany

Pneumologische Praxis am Schloss Charlottenburg Berlin

Berlin, , Germany

Vivantes Klinikum Neukölln

Berlin, , Germany

Vivantes Klinikum Spandau

Berlin, , Germany

Klinikum der Ruhr-Universität Bochum

Bochum, , Germany

Pneumologische Gemeinschaftspraxis Bonn

Bonn, , Germany

Forschungszentrum Borstel

Borstel, , Germany

Klinikum Dortmund gGmbH

Dortmund, , Germany

Universitätsklinikum Dresden

Dresden, , Germany

Pneumologische Klinik Waldhof Elgershausen

Elgershausen, , Germany

Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH

Essen, , Germany

Praxis Dr. med. Ina Itzigehl Euskirchen

Euskirchen, , Germany

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

Universitätsmedizin Greifswald

Greifswald, , Germany

HELIOS Klinik Hagen-Ambrock

Hagen, , Germany

Elbpneumologie Hamburg

Hamburg, , Germany

Schwerpunktpraxis Colonnaden Hamburg

Hamburg, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Thoraxklinik am Universitätsklinikum Heidelberg

Heidelberg, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Lungenfachklinik Immenhausen

Immenhausen, , Germany

Universitätsklinikum Jena

Jena, , Germany

Universitätsklinikum Schleswig-Holstein Kiel

Kiel, , Germany

Universitätsklinikum Schleswig-Holstein Campus Lübeck

Lübeck, , Germany

Brüderkrankenhaus St. Josef Paderborn

Paderborn, , Germany

Diakoniekrankenhaus Rotenburg

Rotenburg (Wümme), , Germany

Krankenhaus Bethanien Solingen

Solingen, , Germany

HELIOS Klinikum Wuppertal-Barmen

Wuppertal, , Germany

Countries

Germany

References

Rohde GG, Koch A, Welte T; ABACOPD study group. Randomized double blind placebo-controlled study to demonstrate that antibiotics are not needed in moderate acute exacerbations of COPD--the ABACOPD study. BMC Pulm Med. 2015 Jan 27;15:5. doi: 10.1186/1471-2466-15-5.

Reference Type: DERIVED

PMID: 25623589 (View on PubMed)

Related Links

http://www.capnetz.de/html/abacopd/project

ABACOPD-Homepage

Other Identifiers

2012-003234-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Protocol-Code: 002/2012

Identifier Type: -

Identifier Source: org_study_id