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

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01892488
• Other study ID #: Protocol-Code: 002/2012
• Secondary ID: 2012-003234-16
• Status: Completed
• Phase: Phase 4
• Start date: June 7, 2013
• Est. completion date: June 5, 2019

Study information

• Verified date: June 2020
• Source: Hannover Medical School
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 295
• Est. completion date: June 5, 2019
• Est. primary completion date: April 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

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.
• 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

Locations

Country	Name	City	State
Germany	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
Germany	Universitätsmedizin Greifswald	Greifswald
Germany	HELIOS Klinik Hagen-Ambrock	Hagen
Germany	Elbpneumologie Hamburg	Hamburg
Germany	Schwerpunktpraxis Colonnaden Hamburg	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
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
Germany	Krankenhaus Bethanien Solingen	Solingen
Germany	HELIOS Klinikum Wuppertal-Barmen	Wuppertal

Sponsors (2)

Lead Sponsor	Collaborator
Hannover Medical School	CAPNETZ Stiftung

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	To evaluate long-term consequences of Placebo treatment	Relapse rate; Time to relapse	up to 1 year
Secondary	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
Secondary	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

External Links

•   ABACOPD-Homepage