Clinical trial NCT01892488: Study to Demonstrate That Antibiotics Are Not Needed in Moderate Acute Exacerbations of COPD
Official title: Randomized Double Blind Placebo-controlled Study to Demonstrate That Antibiotics Are Not Needed in Moderate Acute Exacerbations of COPD - The ABACOPD Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: COPD
AE-COPD
Chronic obstructive pulmonary disease
acute exacerbations of Chronic obstructive pulmonary disease
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
Collaborators: name: CAPNETZ Stiftung
First posted: 2013-07-04
Enrollment: 295
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Additional antibiotic therapy to study medication during treatment period or until the test of cure visit (at day 30)
timeFrame: up to day 30
Secondary outcomes:
measure: To evaluate long-term consequences of Placebo treatment
timeFrame: up to 1 year
measure: To assess patient's clinical improvement relative to treatment
timeFrame: up to 30 days
measure: To assess additional efficacy endpoints and health outcome evaluations
timeFrame: up to 1 year
Other outcomes:
measure: Assessment of safety:
timeFrame: up to 1 year
Locations:
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen
city: Bad Arolsen
country: Germany
facility: Krankenhaus Bad Arolsen
city: Ballenstedt
country: Germany
facility: Lungenklinik Ballenstedt
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Berlin
country: Germany
facility: HELIOS Klinikum Emil von Behring Berlin
city: Berlin
country: Germany
facility: Pneumologische Praxis am Schloss Charlottenburg Berlin
city: Berlin
country: Germany
facility: Vivantes Klinikum Neukölln
city: Berlin
country: Germany
facility: Vivantes Klinikum Spandau
city: Bochum
country: Germany
facility: Klinikum der Ruhr-Universität Bochum
city: Bonn
country: Germany
facility: Pneumologische Gemeinschaftspraxis Bonn
city: Borstel
country: Germany
facility: Forschungszentrum Borstel
city: Dortmund
country: Germany
facility: Klinikum Dortmund gGmbH
city: Dresden
country: Germany
facility: Universitätsklinikum Dresden
city: Elgershausen
country: Germany
facility: Pneumologische Klinik Waldhof Elgershausen
city: Essen
country: Germany
facility: Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
city: Euskirchen
country: Germany
facility: Praxis Dr. med. Ina Itzigehl Euskirchen
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald
city: Hagen
country: Germany
facility: HELIOS Klinik Hagen-Ambrock
city: Hamburg
country: Germany
facility: Elbpneumologie Hamburg
city: Hamburg
country: Germany
facility: Schwerpunktpraxis Colonnaden Hamburg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Thoraxklinik am Universitätsklinikum Heidelberg
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Immenhausen
country: Germany
facility: Lungenfachklinik Immenhausen
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Kiel
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein Campus Lübeck
city: Paderborn
country: Germany
facility: Brüderkrankenhaus St. Josef Paderborn
city: Rotenburg
country: Germany
facility: Diakoniekrankenhaus Rotenburg
city: Solingen
country: Germany
facility: Krankenhaus Bethanien Solingen
city: Wuppertal
country: Germany
facility: HELIOS Klinikum Wuppertal-Barmen
Study officials:
affiliation: CAPNETZ Stiftung
name: Gernot Rohde, Prof. Dr.
role: STUDY_DIRECTOR
affiliation: Hannover Medical School
name: Tobias Welte, Prof.Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.