CRP-guided Antibiotic Treatment in COPD Exacerbations Admitted to the Hospital

NCT ID: NCT01232140

Last Updated: 2012-03-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2013-07-31

Brief Summary

Rationale: Acute exacerbations are key events in chronic obstructive pulmonary disease (COPD), resulting in poorer quality of life. Causes include irritants, viruses and bacterial pathogens. These exacerbations are often treated with a combination of corticosteroids, bronchodilators and antibiotics, but the benefit of antibiotic therapy remains controversial. Several trials studying antibiotic treatment in AECOPD showed conflicting data, with several large studies failing to demonstrate superiority of antibiotic therapy over placebo. Other trials indicated that antibiotic therapy is effective in patients who have at least two of the following symptoms: increased dyspnoea, increased sputum volume and increased sputum purulence. Ever since sputum purulence has been used as a predictive marker in AECOPD, a strategy that has been integrated in the GOLD guideline for treatment of AECOPD. However, the color of sputum reported by patients is not always reliable and inspection of sputum is not always possible. Several serum biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) are now available. In a recent trial of doxycycline in addition to systemic corticosteroids for patients hospitalized with AECOPD we found that CRP might be valuable as a marker predictive of response to antibiotic treatment in AECOPD.

Detailed Description

Objective: CRP-guided antibiotic therapy will be compared with standard antibiotic therapy in AECOPD. Our aim is that CRP guided therapy will lead to 20% reduction in antibiotic consumption.

Study design: randomized controlled intervention trial Study population: Hospitalised COPD patients with acute exacerbation. Intervention (if applicable): Patients with type 1 and 2 exacerbation will be assigned to either CRP guided therapy or antibiotic therapy according to GOLD guidelines.

Main study parameters/endpoints: The main endpoint of the study is the reduction in antibiotic consumption. Furthermore, the real incidence of infiltrates in AECOPD with fever will be studied. As secondary outcome the objectives length of hospitalization, time to treatment failure within 30-days and time to next exacerbation will be assessed. The relation between the level of biomarkers the presence of infiltrates on the HRCT will be investigated.

Subjective improvement in symptoms will be measured by symptoms (VAS-LRTI) and quality of life will be assessed by St George's Respiratory Questionnaire. Finally, adverse effects of the antibiotic treatment will be recorded.

In order to observe a significant difference of antibiotic consumption, 60% in standard antibiotic group and 40% in CRP guided antibiotic group, with a power of 0.8, a total of 110 patients have to be assigned by randomisation to each group.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients in both treatment arms will receive a non-experimental treatment. Both treatment options are recognized as part of standard care. The burden associated with participation is limited to a total of 3 visits to the hospital and phone call for data assessment at regular follow-up. There are no specific risks involved in participating. Less adverse effects may be beneficially for the patient.

Conditions

COPD; Exacerbation; Bronchitis; Sputum; C-Reactive Protein

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CRP-guided antibiotic treatment

If CRP\> 50 mg/l a patient receive antibiotic treatment, whereas in those patients with CRP =\< 50 mg/l antibiotic treatment is withheld.

Group Type: EXPERIMENTAL

CRP-guided antibiotic treatment

Intervention Type: OTHER

If CRP\> 50 mg/l patients with AECOPD receive antibiotic treatment, whereas in those patients with CRP =\< 50 mg/l antibiotic treatment are withheld. This will be compared to the regular antibiotic treatment that has been advised by the GOLD strategy

GOLD strategy-antibiotic treatment

According to the GOLD strategy a patient with an AECOPD should prescribed antibiotic treatment if a patient has symptoms of increased dyspnea, increased sputum production and change of sputum color. Two of these three criteria should be present, however change in sputum production is obligatory.

Group Type: OTHER

CRP-guided antibiotic treatment

Intervention Type: OTHER

If CRP\> 50 mg/l patients with AECOPD receive antibiotic treatment, whereas in those patients with CRP =\< 50 mg/l antibiotic treatment are withheld. This will be compared to the regular antibiotic treatment that has been advised by the GOLD strategy

Interventions

CRP-guided antibiotic treatment

If CRP\> 50 mg/l patients with AECOPD receive antibiotic treatment, whereas in those patients with CRP =\< 50 mg/l antibiotic treatment are withheld. This will be compared to the regular antibiotic treatment that has been advised by the GOLD strategy

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age 40 or over. No upper age limit will be employed.
• Written informed consent obtained.
• AECOPD according to the GOLD guideline. An exacerbation of COPD is defined as an event in the natural course of the disease characterized by a change in the patient's baseline dyspnoea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a change in regular medication in a patient with underlying COPD.
• Criteria for hospital admission according to the GOLD: marked increase in symptoms (i.e. resting dyspnoea), severe underlying COPD, onset of new physical signs (cyanosis, edema), failure to respond to initial medical management, significant co morbidities, frequent exacerbations, newly occurring arrhythmias, diagnostic uncertainty.
• Former of current smoker with a minimum smoking history of 10 pack years.
• Patients have to be capable of ingesting oral medication.
• Patients have to be mentally capable of participating in the study (able to complete questionnaires and perform lung function tests).
• Life expectancy ≥ 30 days.

Exclusion Criteria

• Pregnant or lactating women, or women of childbearing age not using an acceptable method of contraception.
• Pretreatment with corticosteroids (cumulative dose >210 mg) for the present exacerbation.
• Progression or new radiographic abnormalities on the chest X-ray or CT scan compatible with pneumonia.
• bronchiectasis (HRCT confirmed).
• Cystic fibrosis.
• Tuberculosis.
• Immunodeficiency disorders such as AIDS, humoral immune defect, ciliary dysfunction etc., and the use of immunosuppressive drugs (>30 mg prednisolone/day maintenance dose or equivalent for more than 4 weeks).
• Recent or unresolved lung malignancy.
• Other disease likely to require antibiotic therapy, such as recurrent sinusitis or urinary tract infection.
• Significant gastrointestinal or other conditions that may affect study drug absorption.
• Class III or IV congestive heart failure or stroke.
• Newly diagnosed pulmonary embolism

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

Sponsors

Medical Center Alkmaar

OTHER

Sponsor Role: lead

Responsible Party

W.G.Boersma

PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

W.G. Boersma, PHD,MD

Role: STUDY_DIRECTOR

Medical Centre Alkmaar

Locations

W.G.Boersma

Alkmaar, North Holland, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Facility Contacts

W.G. Boersma, PHD,MD

Role: primary

w.boersma@mca.nl

0031-725482750

J.M.A. Daniels, PHD, MD

Role: backup

j.daniels@vumc.nl

0031204444444

References

Daniels JM, Snijders D, de Graaff CS, Vlaspolder F, Jansen HM, Boersma WG. Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2010 Jan 15;181(2):150-7. doi: 10.1164/rccm.200906-0837OC. Epub 2009 Oct 29.

Reference Type: RESULT

PMID: 19875685 (View on PubMed)

Prins HJ, Duijkers R, Daniels JMA, van der Molen T, van der Werf TS, Boersma W. COPD-Lower Respiratory Tract Infection Visual Analogue Score (c-LRTI-VAS) validation in stable and exacerbated patients with COPD. BMJ Open Respir Res. 2021 Feb;8(1):e000761. doi: 10.1136/bmjresp-2020-000761.

Reference Type: DERIVED

PMID: 33593795 (View on PubMed)

Prins HJ, Duijkers R, Lutter R, Daniels JM, van der Valk P, Schoorl M, Kerstjens HA, van der Werf TS, Boersma WG. Blood eosinophilia as a marker of early and late treatment failure in severe acute exacerbations of COPD. Respir Med. 2017 Oct;131:118-124. doi: 10.1016/j.rmed.2017.07.064. Epub 2017 Aug 1.

Reference Type: DERIVED

PMID: 28947018 (View on PubMed)

Other Identifiers

CATCH study

Identifier Type: -

Identifier Source: org_study_id

AECOPD

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id