Clinical trial NCT01125098: Comparison of a Serum PRO-CT Guided Treatment and the Recommended Antibiotic Treatment for COPD
Official title: Comparison of a Serum Procalcitonin (PRO-CT) Guided Treatment Plan With the Standard Guideline Recommended Antibiotic Treatment Plan for Patients Hospitalized With a Diagnosis of Exacerbation of COPD
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
PRO-CT
antibiotics
Lead sponsor: University of Modena and Reggio Emilia
Sponsor class: OTHER
Collaborators: name: Agenzia Italiana del Farmaco
First posted: 2010-05-18
Enrollment: 183
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with diagnosis of COPD according to GOLD guidelines

Brief summary: Exacerbations of chronic obstructive pulmonary disease (COPD) are the first cause of admission to Pulmonary Department in Italy and worldwide. Guidelines recommend treating most patients hospitalized for exacerbations of COPD with antibiotics, even if the role of bacterial infection is often uncertain and the effect of antibiotics poor. The recommendation to use antibiotics is guided by clinical signs and symptoms that have an insufficient diagnostic accuracy, whereas serum biomarkers as procalcitonin (PRO-CT) may guide the selection of COPD patients who need antibiotic treatment. The main aim of the study is to investigate whether antibiotics can be safely stopped after 3 days or continued for 10 days according to a PRO-CT-guided algorithm in patients hospitalized for exacerbations of COPD for whom guidelines recommend 3-10 days antibiotic treatment based on presence of increased dyspnoea, sputum and purulence. The study is designed to assess the non inferiority of the PRO-CT guided plan as compared to the standard guideline recommended plan. The PRO-CT guided withholding of antibiotics is viewed as an experimental intervention associated with less antibiotic-associated complications, eg antibiotic resistance and drug-related side-effect and lower costs. The proposed study is a prospective, randomised controlled, single-blinded intervention trial comparing the standard with a PRO-CT guided antibiotic treatment plan. Patients will be recruited from the Pulmonary Department of 18 University or City Hospitals in Italy, starting October 2006 and continuing until December 2010. Results expected by end of 2011. The 100 patients randomised to the standard non PRO-CT guided antibiotic treatment plan will continue antibiotics for 10 days, whereas the 100 patients randomised to the PRO-CT guided antibiotic treatment plan will continue for 10 days or stop antibiotics on day 3 depending on PRO-CT levels measured at admission, day 1 and day 2. Serum PRO-CT will be measured in a central laboratory. Patients will be examined at admission, discharge, 10 days, 1, 3 and 6 months. A telephone interview will be obtained at 2, 4 and 5 months. The primary outcome of the study will be the rate of exacerbations. Secondary outcomes will be hospital readmission, admission to ICU, change in FEV1, duration of hospitalization, and death. The sample size was estimated according to the primary outcome of the study.

Detailed description: Patients will be recruited from the Pulmonary Department of 18 University or City Hospitals in Italy, starting October 2006 and continuing until December 2010. The 100 patients randomised to the standard non PRO-CT guided antibiotic treatment plan will continue antibiotics for 10 days, whereas the 100 patients randomised to the PRO-CT-guided antibiotic treatment plan will continue for 10 days or stop antibiotics on day 3 depending on PRO-CT levels measured at admission, day 1 and day 2. Serum PRO-CT will be measured in a central laboratory. Patients will be examined at admission (visit 1), discharge and/or at 10 days (visit 4), 1 (visit 5), 3 (visit 6) and 6 months (visit 7). A telephone interview will be obtained at 2, 4 and 5 months. The primary outcome of the study will be the rate of exacerbations. Secondary outcomes will be hospital readmission, admission to ICU, change in FEV1, duration of hospitalization, and death. The sample size was estimated according to the primary outcome of the study.

Eligibility criteria: Inclusion Criteria:

* Male and female patients who give written informed consent
* Age: adults \>18 years old
* COPD diagnosis according to GOLD guidelines: FEV1/FVC \<70% with FEV1\<80% of predicted. If a COPD diagnosis is not evident from previous spirometric exams of the patient, a new spirometry will be obtained within 3 days of admission and a diagnosis of COPD will be made if all of the following conditions are true: 1) FEV1/FVC \<70% with FEV1 \<80% of predicted; 2) history of cigarette smoking; 3) exclusion of bronchial asthma diagnosis. At the end of the study (i.e. at 6 months) a new spirometric exam will be obtained from these patients to confirm the new diagnosis of COPD made at admission.
* Diagnosis of COPD exacerbation:

  * defined as acute-onset dyspnoea and/or cough associated with increased purulent sputum production (ANTHONISEN criteria)
  * requiring, according to guidelines (GOLD 2005), treatment with antibiotic
  * requiring hospitalization

Exclusion Criteria:

* Female subjects: pregnant, lactating mother or lack of efficient contraception in a subject with child-bearing potential (e.g. contraceptive methods other than oral contraceptives, IUD, tubal ligation)

  * Diagnosis of bronchial asthma
  * Coexisting medical conditions: unstable concomitant cardiovascular, renal, hepatic, gastrointestinal, neurological, endocrine, metabolic, muscle-skeletal, neoplastic, respiratory or other clinically significant disease (patients with stable and well controlled hypertension or diabetes may be included in the study)
  * Clinical significant laboratory abnormalities indicating unstable concomitant disease
  * Patients in whom survival for at least 1 year is unlikely
  * Inability to give informed consent

Primary outcomes:
measure: To Evaluate the Rate of Severe Exacerbations in COPD, Comparing COPD Patients Previously Treated According to the PRO-CT Protocol Versus COPD Patients Previously Treated With Standard Antibiotic Therapy.
timeFrame: 6 months
Secondary outcomes:
measure: Cost/Effectiveness of the Use of PRO-CT-guided Decision Making Protocol on Duration of Antibiotic Therapy in COPD Exacerbations.
timeFrame: Discharge /10 days-6 months
measure: To Evaluate if the PRO-CT-guided Decision Making to Shorten Antibiotic Therapy is Less Effective Than the Guideline Recommended Standard Antibiotic Treatment in Preventing Hospitalization.
timeFrame: Discharge/10 days-6 months
measure: To Verify Survival in COPD Patients Comparing to Those Treated According to the PRO-CT Protocol Versus COPD Patients Treated With Standard Antibiotic Therapy.
timeFrame: Discharge/10 days-6 months
measure: To Verify Changes in FEV1 Value in COPD Patients Comparing Those Treated According to the PRO-CT Protocol Versus COPD Patients Treated With Standard Antibiotic Therapy.
timeFrame: Discharge/10 days-6 months
measure: To Verify the Duration of Hospitalization for Severe Exacerbation in COPD Patients Treated According to the PRO-CT Protocol Versus COPD Patients Treated With Standard Antibiotic Therapy.
timeFrame: Discharge/10 days-6 months
Other outcomes:
Locations:
city: Modena
country: Italy
facility: University of Modena and Reggio Emilia
Study officials:
affiliation: University of Modena and Reggio Emilia
name: Leonardo M Fabbri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Verduri A, Luppi F, D'Amico R, Balduzzi S, Vicini R, Liverani A, Ruggieri V, Plebani M, Barbaro MP, Spanevello A, Canonica GW, Papi A, Fabbri LM, Beghe B; FARM58J2XH Study Group. Antibiotic treatment of severe exacerbations of chronic obstructive pulmonary disease with procalcitonin: a randomized noninferiority trial. PLoS One. 2015 Mar 11;10(3):e0118241. doi: 10.1371/journal.pone.0118241. eCollection 2015.