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

Randomized Double Blind Placebo-controlled Study to Demonstrate That Antibiotics Are Not Needed in Moderate Acute Exacerbations of COPD - The ABACOPD Study

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).

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: Placebo; Drug: Sultamicillin

• Study Type: Interventional
• Enrollment (Actual): 295
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany
    • Universitätsklinikum Aachen
  • Bad Arolsen, Germany
    • Krankenhaus Bad Arolsen
  • Ballenstedt, Germany
    • Lungenklinik Ballenstedt
  • Berlin, Germany
    • Charité - Universitätsmedizin Berlin
  • Berlin, Germany
    • Vivantes Klinikum Neukölln
  • Berlin, Germany
    • Vivantes Klinikum Spandau
  • Berlin, Germany
    • HELIOS Klinikum Emil von Behring Berlin
  • Berlin, Germany
    • Pneumologische Praxis am Schloss Charlottenburg Berlin
  • Bochum, Germany
    • Klinikum der Ruhr-Universität Bochum
  • Bonn, Germany
    • Pneumologische Gemeinschaftspraxis Bonn
  • Borstel, Germany
    • Forschungszentrum Borstel
  • Dortmund, Germany
    • Klinikum Dortmund gGmbH
  • Dresden, Germany
    • Universitätsklinikum Dresden
  • Elgershausen, Germany
    • Pneumologische Klinik Waldhof Elgershausen
  • Essen, Germany
    • Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
  • Euskirchen, Germany
    • Praxis Dr. med. Ina Itzigehl Euskirchen
  • Freiburg, Germany
    • Universitätsklinikum Freiburg
  • Greifswald, Germany
    • Universitätsmedizin Greifswald
  • Hagen, Germany
    • HELIOS Klinik Hagen-Ambrock
  • Hamburg, Germany
    • Elbpneumologie Hamburg
  • Hamburg, Germany
    • Schwerpunktpraxis Colonnaden Hamburg
  • Hannover, Germany
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany
    • Universitätsklinikum Heidelberg
  • Heidelberg, Germany
    • Thoraxklinik am Universitatsklinikum Heidelberg
  • Immenhausen, Germany
    • Lungenfachklinik Immenhausen
  • Jena, Germany
    • Universitatsklinikum Jena
  • Kiel, Germany
    • Universitätsklinikum Schleswig-Holstein Kiel
  • Lübeck, Germany
    • Universitätsklinikum Schleswig-Holstein Campus Lübeck
  • Paderborn, Germany
    • Brüderkrankenhaus St. Josef Paderborn
  • Rotenburg, Germany
    • Diakoniekrankenhaus Rotenburg
  • Solingen, Germany
    • Krankenhaus Bethanien Solingen
  • Wuppertal, Germany
    • HELIOS Klinikum Wuppertal-Barmen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: lactose pill; Placebo for 5 days as supplement to standard of care for patients with AE-COPD	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; Other Names: Placebo: Lactose pill
Experimental: 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	Drug: 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.; Other Names: aminopenicillin + betalactamase inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional antibiotic therapy to study medication during treatment period or until the test of cure visit (at day 30)	Assessment of additional antibiotic therapy: Patients will be asked at every visit about use of additional antibiotic therapy. In the case of use of additional antibiotic therapy the exact starting date, the active compound, the dose administered, the route of administration,the length of treatment and the indication will be registered. Only additional antibiotic therapy for AE-COPD will be counted as treatment failure.	up to day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate long-term consequences of Placebo treatment	Relapse rate; Time to relapse	up to 1 year
To assess patient's clinical improvement relative to treatment	Clinical cure rate at the "end of therapy visit" (at day 6); Clinical cure rate at the "test Of cure visit" (at day 30) (both determined by patient-centered outcomes (diary cards))	up to 30 days
To assess additional efficacy endpoints and health outcome evaluations	Changes in COPD Assessment Test(CAT); Changes in Exacerbations of Chronic Pulmonary Disease Tool-Patient reported outcome (EXACT-PRO); Additional antibiotic therapy; Time to next exacerbation; Number of exacerbations during follow up; Per-subject relapse rate at the LFU (Late Follow Up) visits in the subset of subjects in the CE population who were clinically cured at the TOC visit; Changes in length of stay in hospital for hospitalized patients; All cause mortality	up to 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of safety:	Key criteria for safety are: adverse events, serious adverse events, changes in physical examination, vital signs, laboratory tests	up to 1 year

Collaborators and Investigators

• Sponsor: Hannover Medical School
• Collaborators: CAPNETZ Stiftung
• Investigators: Study Director: Gernot Rohde, Prof. Dr., CAPNETZ Stiftung; Principal Investigator: Tobias Welte, Prof.Dr., Hannover Medical School

Publications and helpful links

General Publications

• 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.

Helpful Links

• ABACOPD-Homepage

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2013
• Primary Completion (Actual): April 23, 2019
• Study Completion (Actual): June 5, 2019

Study Registration Dates

• First Submitted: June 27, 2013
• First Submitted That Met QC Criteria: July 1, 2013
• First Posted (Estimate): July 4, 2013

Study Record Updates

• Last Update Posted (Actual): June 5, 2020
• Last Update Submitted That Met QC Criteria: June 4, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: COPD; Chronic obstructive pulmonary disease; AE-COPD; acute exacerbations of Chronic obstructive pulmonary disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; beta-Lactamase Inhibitors; Sultamicillin
• Other Study ID Numbers: Protocol-Code: 002/2012; 2012-003234-16 (EudraCT Number)