OBJECTIVESIn this study CRP-guided antibiotic therapy will be compared with GOLD antibiotic therapy in AECOPD with special attention at consumption antibiotics and treatment failure.
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameter/endpoint
Reduction in antibiotic treatment prescribed in the CRP guided therapy during
the period of 30 days after entering the study. Incidence of pulmoanary
infiltrates on CT scan in patients with AECOPD.
Secondary outcome
1. The effect of treatment will be estimated by comparing the percentage of
treatment failure at day 30.
2. Time to next exacerbation reported at 3, 6, and 12 months follow-up.
3. Length of hospital stay.
4. Symptom scores (VAS-LRTI) on admission, day 14, at day 30.
5. Quality of life (Clinical COPD Questionnaire) on admission, 30 days.
6. Adverse effects of treatment (days 1-10 and day 30).
7. The relation between biomarkers (CRP,PCT) and pulmonary
infiltrates observed on CT-scan.
Background summary
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. Sputum purulence is most
discriminating variable for the prescription of antibiotic treatment. However,
the color of sputum reported by patients is not always reliable. In previous
study we have demonstrated that CRP may more accurate predict who may benefit
from antibiotic
therapy or not.
Objective: CRP-guided antibiotic therapy will be compared with antibiotic
therapy according to the GOLD strategy in AECOPD. Our aim is that CRP guided
therapy will lead to 20% reduction in antibiotic consumption at day 10.
Study design: randomized controlled intervention trial
Study population: Hospitalised COPD patients with acute exacerbation.
Intervention (if applicable): Patients with AECOPD will be assigned to either
CRP guided therapy or antibiotic therapy according to the GOLD strategy, that
means two of three symptoms should be present: increased dyspnoe and/or
increased sputumproduction and at least change of sputum color.
Main study parameters/endpoints: The main endpoint of the study is the
reduction in antibiotic consumption at day 10. Furthermore, the real incidence
of infiltrates in AECOPD 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. Subjective improvement in quality of life
will be measured by symptoms (VAS-LRTI) and disease-specific (Clinical COPD
Questionnaire[CCQ]) quality of life instruments. Finally, adverse effects of
the antibiotic treatment will be recorded.The relation between the level of
biomarkers the presence of infiltrates on the low dose CT will be compared .
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 220 women 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.
Study objective
OBJECTIVES
In this study CRP-guided antibiotic therapy will be compared with GOLD
antibiotic therapy in AECOPD with special attention at consumption antibiotics
and treatment failure.
Study design
STUDY DESIGN
The present study will be prospectively performed using the following study
design: A randomized controlled intervention trial. Patients admitted at the
Medical Centre Alkmaar or Medical Spectrum Twente with an acute exacerbation of
COPD are asked to participate the study. After informed consent patients will
be randomized in 2 groups, namely CRP-guided (cut-off 50 mg/L) antibiotic
therapy (group 1) versus GOLD antibiotic therapy (group 2). Patients with CRP >=
50 mg/L receive antibiotic treatment, whereas in patients with CRP< 50 mg/L
antibiotic treatment will be withheld. All patients randomized in group 2
receive antibiotic treatment if two of three symptoms such as increased dyspnoe
and/or increased sputumproduction and at least change of sputum color are
present. The type antibiotic treatment is standardized. All other co-medication
for ACEOPD in both groups are also standardized (corticosteroids and
bronchodilators). All other treatment (oxygen, physiotherapy,etc.) will be
standardized as accurate as possible. We expect that CRP-guided therapy will be
as good as standard antibiotic treatment, that means that patients with CRP <
50 mg/L can be safely treated without antibiotic treatment.
Intervention
Study procedures
Patients admitted at the hospital with an AECOPD will be asked to participate
by residents and pulmonologists. After checking the inclusion and exclusion
criteria a patient/ relative is asked to participate. The patient/relative will
receive written and verbal information about the study. If the patient/relative
wants to cooperate he or she is asked to sign the informed consent.
Subsequently, the patient will be randomized in of the two groups. Routine
diagnostic tests, such as laboratory examination, ECG, chest X-ray, and
arterial blood gas analysis will be performed at admission. Treatment is
initiated immediately, including antibiotic treatment accept in those patients
with CRP < 50 mg/L where antibiotic treatment is withheld (group 1). Patients
of group 2 are not treated with antibiotics if they do not fulfill the critera
for bacterial infection. If possible. sputum will be obtained before antibiotic
treatment is started. When a patient is substantially improved, he or she will
discharged from the hospital. Outpatient visits are scheduled at 30 days, 3
months, 6 months and 12 months(by phone) follow-up.
Study burden and risks
We expect that patients with bacterial AECOPD can be treated more efficiently.
Our aim is, that viral infection or a low grade bacterial infection is
associated with a low level of CRP. These AECOPD do respond better on treatment
with corticosteroids than antibiotic treatment. Moreover, antibiotic treatment
may induce adverse effects, such gastro intestinal disturbances and allergic
reactions. By systematically prescribing antibiotic drugs in patients with
AECOPD, antibiotic pressure in the hospital is increasing and has a negative
effect on the development of resistant bacteria.
All patients will be carefully monitored, and therefore the risk withholding an
antibiotic in episode of worsening AECOPD is negligible. The non-intervention
group will be treated as usual.
Wilhelminalaan 12
Alkmaar 1815JD
NL
Wilhelminalaan 12
Alkmaar 1815JD
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria:
• Age 40 or over. No upper age limit will be employed.
• Written informed consent obtained.
• 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.
• Patients have to be capable of ingesting oral medication.
• Patients have to mentally capable of participating in the study (able to complete questionnaires and perform lung function tests).
• Life expectancy >= 30 days.
• Smoking history > 10 packyears
Exclusion criteria
Exclusion criteria
• Pregnant or lactating women
• Pretreatment with corticosteroids (cumulative dosis >210 mg) for the present exacerbation.
• Progression or new radiographic abnormalities on the chest X-ray.
• Bronchiectasis (HRCT confirmed).
• Cystic fibrosis
• Tuberculosis
• Immunodeficiency disorders such as AIDS, humoral immune deficiency, ciliary dysfunction etc., and the use of immunosuppressive drugs (>30 mg prednisolone 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
• Chonic incresead CRP of any cause (history, lab exam)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT01232140 |
| CCMO | NL33284.094.10 |