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

This study has been completed.
Sponsor:
Collaborator:
Agenzia Italiana del Farmaco
Information provided by (Responsible Party):
Leonardo M. Fabbri, University of Modena and Reggio Emilia
ClinicalTrials.gov Identifier:
NCT01125098
First received: April 13, 2010
Last updated: February 1, 2013
Last verified: February 2013
History of Changes
  Purpose

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.


Condition Intervention
Chronic Obstructive Pulmonary Disease
 Other: PRO-CT values

Study Type: Observational
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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Modena and Reggio Emilia:

Primary Outcome Measures:
  • 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. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Number of severe exacerbations in COPD patients, initially randomized in the study population.


Secondary Outcome Measures:
  • Cost/effectiveness of the use of PRO-CT-guided decision making protocol on duration of antibiotic therapy in COPD exacerbations. [ Time Frame: Discharge /10 days-6 months ] [ Designated as safety issue: Yes ]
  • 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 hospital admission for severe COPD exacerbation. [ Time Frame: Discharge/10 days-6 months ] [ Designated as safety issue: Yes ]
    Number of hospital re-admissions among COPD patients of the study population.

  • To verify survival in COPD patients comparing those treated according to the PRO-CT protocol versus COPD patients treated with standard antibiotic therapy. [ Time Frame: Discharge/10 days-6 months ] [ Designated as safety issue: Yes ]
    Number of deaths from any cause among COPD patients in the study population.

  • 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. [ Time Frame: Discharge/10 days-6 months ] [ Designated as safety issue: Yes ]
    COPD patients of the study population will undergo spirometry on visit 1, 4, 5, 7.

  • 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. [ Time Frame: Discharge/10 days-6 months ] [ Designated as safety issue: Yes ]
    Duration in days in case of hospitalization for severe exacerbation in COPD patients, initially randomized in the study population.


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.


Enrollment: 183
Study Start Date: October 2006
Study Completion Date: December 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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
  • 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.
Other Name: Amoxicilline + Clavulanate OR Quinolones
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.

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

Ages Eligible for Study:   18 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with diagnosis of COPD according to GOLD guidelines

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01125098

Locations
Italy
University of Modena and Reggio Emilia
Modena, Italy, 41100
Sponsors and Collaborators
University of Modena and Reggio Emilia
Agenzia Italiana del Farmaco
Investigators
Principal Investigator: Leonardo M Fabbri, MD University of Modena and Reggio Emilia
  More Information

No publications provided

Responsible Party: Leonardo M. Fabbri, Professor Medical Doctor, University of Modena and Reggio Emilia
ClinicalTrials.gov Identifier: NCT01125098     History of Changes
Other Study ID Numbers: FARM58J2XH
Study First Received: April 13, 2010
Last Updated: February 1, 2013
Health Authority: Italy: Ethics Committee

Keywords provided by University of Modena and Reggio Emilia:
COPD
PRO-CT
antibiotics

Additional relevant MeSH terms:
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Anti-Bacterial Agents
 Amoxicillin-Potassium Clavulanate Combination
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 21, 2013