Comparison of a Serum PRO-CT Guided Treatment and the Recommended Antibiotic Treatment for COPD

NCT ID: NCT01125098

Last Updated: 2014-12-17

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 183 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2011-12-31

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; PRO-CT; antibiotics

Study Groups

PRO-CT group: Experimental

COPD patients in the PRO-CT group will continue or discontinue antibiotic therapy depending on PRO-CT values.

PRO-CT values

Intervention Type: OTHER

• continue antibiotics for 10 days if a single PRO-CT value is 0.25 mcg/L or greater, that will be judged suggestive of bacterial infection
• continue antibiotics from day 3 to day 10 if one or more PRO-CT values are 0.1 to 0.25 mcg/L, indicative of possible bacterial infection, PLUS acute respiratory failure or clinical instability
• stop antibiotics on day 3, if one or more PRO-CT values are between 0.1 to 0.25 mcg/L, indicative of possible bacterial infection, BUT the patient has not acute respiratory failure or clinical instability
• stop antibiotics if all the PRO-CT values are < 0.1 mcg/L or if there is a consistent trend to normalization of PRO-CT with the last value < 0.1 mcg/L, that will be judged suggestive of absence of bacterial infection.

Standard group: No intervention

COPD patients in the Standard group will continue antibiotic therapy for 10 days according to guidelines recommended treatment plan in case of COPD exacerbations.

No interventions assigned to this group

Interventions

PRO-CT values

• continue antibiotics for 10 days if a single PRO-CT value is 0.25 mcg/L or greater, that will be judged suggestive of bacterial infection
• continue antibiotics from day 3 to day 10 if one or more PRO-CT values are 0.1 to 0.25 mcg/L, indicative of possible bacterial infection, PLUS acute respiratory failure or clinical instability
• stop antibiotics on day 3, if one or more PRO-CT values are between 0.1 to 0.25 mcg/L, indicative of possible bacterial infection, BUT the patient has not acute respiratory failure or clinical instability
• stop antibiotics if all the PRO-CT values are < 0.1 mcg/L or if there is a consistent trend to normalization of PRO-CT with the last value < 0.1 mcg/L, that will be judged suggestive of absence of bacterial infection.

Intervention Type: OTHER

Other Intervention Names

Amoxicilline + Clavulanate OR Quinolones

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 95 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Agenzia Italiana del Farmaco

OTHER_GOV

Sponsor Role: collaborator

University of Modena and Reggio Emilia

OTHER

Sponsor Role: lead

Responsible Party

Leonardo M. Fabbri

Professor Medical Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Leonardo M Fabbri, MD

Role: PRINCIPAL_INVESTIGATOR

University of Modena and Reggio Emilia

Locations

University of Modena and Reggio Emilia

Modena, , Italy

Countries

Italy

References

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.

Reference Type: DERIVED

PMID: 25760346 (View on PubMed)

Other Identifiers

FARM58J2XH

Identifier Type: -

Identifier Source: org_study_id