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

NCT01125098 | Completed Results

• 1 other identifier: FARM58J2XH
• Study Type: observational
• Target: 183
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; PRO-CT; antibiotics

Outcome Measures

Primary Outcomes (1)

• 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.

  We prospectively recruited COPD patients hospitalized for severe exacerbation of COPD and followed them after discharge. The primary end point of the study was the number of patients with at least 1 exacerbation at 6 months after the index exacerbation that was the reason for their hospital admission.

  6 months

Secondary Outcomes (5)

• Cost/Effectiveness of the Use of PRO-CT-guided Decision Making Protocol on Duration of Antibiotic Therapy in COPD Exacerbations.

  Discharge /10 days-6 months

• 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.

  Discharge/10 days-6 months

• To Verify Survival in COPD Patients Comparing to Those Treated According to the PRO-CT Protocol Versus COPD Patients Treated With Standard Antibiotic Therapy.

  Discharge/10 days-6 months

• 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.

  Discharge/10 days-6 months

• 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.

  Discharge/10 days-6 months

Study Arms (2)

PRO-CT group: Experimental

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

Other: PRO-CT values

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.

Interventions

PRO-CT values 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.

Also known as: Amoxicilline + Clavulanate OR Quinolones

PRO-CT group: Experimental

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with diagnosis of COPD according to GOLD guidelines

You may qualify if:

• Male and female patients who give written informed consent
• Age: adults \>18 years old
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Modena and Reggio Emilia: lead
• Agenzia Italiana del Farmaco: collaborator

Study Sites (1)

University of Modena and Reggio Emilia

Modena, 41100, Italy

Location

Related Publications (1)

• 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.

  PMID: 25760346 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples and sputum will be collected from COPD patients in order to measure serum PRO-CT levels and inflammatory markers (cells and mediators), respectively.

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Amoxicillin; Clavulanic Acid; Quinolones

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Clavulanic Acids; Quinolines

Results Point of Contact

• Title: Leonardo Fabbri
• Organization: Department of Oncology Haematology and Respiratory Diseases

leonardo.fabbri@unimore.it

+39 059422

Study Officials

• Leonardo M Fabbri, MD

  University of Modena and Reggio Emilia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Medical Doctor

Study Record Dates

• First Submitted: April 13, 2010
• First Posted: May 18, 2010
• Study Start: October 1, 2006
• Primary Completion: July 1, 2011
• Study Completion: December 1, 2011
• Last Updated: December 17, 2014
• Results First Posted: December 17, 2014

Record last verified: 2014-12

Locations

IT (1)