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A Randomized Double-Blinded, Placebo-Controlled Trial of Antibiotic Therapy in Patients With Lower Respiratory Tract Infection (LRTI) and a Procalcitonin Level

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ClinicalTrials.gov Identifier: NCT03341273
Recruitment Status : Recruiting
First Posted : November 14, 2017
Last Update Posted : April 13, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
This is a randomized, double-blinded, placebo-controlled, non-inferiority multicenter clinical trial of azithromycin vs. placebo in adults presenting as outpatients with suspect LRTI and a PCT level of < /=0.25 ng/mL, as a strategy for reducing antibiotic prescriptions. The study is designed to compare the efficacy of azithromycin versus placebo on Day 5 (i.e., after 4 days of treatment) in subjects with suspect LRTI and PCT levels of < /=0.25 ng/mL at enrollment using a non-inferiority approach. The study will recruit potential subjects 18 years of age or older who are suspected to have LRTI and 420 subjects will be randomized 1:1 to receive oral azithromycin or placebo for five days. Randomized subjects will have efficacy measured from the time of the first dose of study drug (Day 1) through approximately Day 28. The Primary Objective is to compare the efficacy of azithromycin versus placebo on Day 5 (i.e., after 4 days of treatment) in subjects with suspect LRTI and PCT levels of < /=0.25 ng/mL at enrollment using a non-inferiority approach.

Condition or disease Intervention/treatment Phase
Lower Respiratory Tract Infection Drug: Azithromycin Other: Placebo Device: VIDAS B.R.A.H.M.S Procalcitonin Test (PCT) Not Applicable

Detailed Description:
This is a randomized, double-blinded, placebo-controlled, non-inferiority multicenter clinical trial of azithromycin vs. placebo in adults presenting as outpatients with suspect LRTI and a PCT level of < /=0.25 ng/mL, as a strategy for reducing antibiotic prescriptions. The study is designed to compare the efficacy of azithromycin versus placebo on Day 5 (i.e., after 4 days of treatment) in subjects with suspect LRTI and PCT levels of < /=0.25 ng/mL at enrollment using a non-inferiority approach. The study will recruit potential subjects 18 years of age or older who are suspected to have LRTI and 420 subjects will be randomized 1:1 to receive oral azithromycin or placebo for five days. Randomized subjects will have efficacy measured from the time of the first dose of study drug (Day 1) through approximately Day 28. The Primary Objective is to compare the efficacy of azithromycin versus placebo on Day 5 (i.e., after 4 days of treatment) in subjects with suspect LRTI and PCT levels of < /=0.25 ng/mL at enrollment using a non-inferiority approach. The Secondary Objectives are to compare: groups receiving azithromycin versus placebo with regard to all antibiotic use by Days 11 and 28; groups receiving azithromycin versus placebo with regard to return visits to a physician's office or urgent care by Days 11 and 28; groups receiving azithromycin versus placebo with regard to emergency department visits by Days 11 and 28; groups receiving azithromycin versus placebo with regard to hospitalization by Days 11 and 28 if not hospitalized at the enrollment and randomization visit; groups receiving azithromycin versus placebo with regard to improvement in presenting symptoms by Days 11 and 28; the efficacy of azithromycin versus placebo in subjects with suspected LRTI and PCT levels of < /=0.25 ng/mL at Day 5 using a superiority approach, employing the "Response Adjusted for Days of Antibiotic Risk (RADAR)" methodology; groups receiving azithromycin versus placebo in regard to solicited events by Day 5; groups receiving azithromycin versus placebo in regard to hospitalization or visits to an ED, outpatient clinic, or urgent care center for worsening or persistent LRTI after randomization by Day 5; groups receiving azithromycin versus placebo in regard to improvement in vital sign abnormalities or symptoms present at enrollment, on Day 5; groups receiving azithromycin versus placebo in regard to new vital sign abnormalities or symptoms on Day 5, or deterioration in symptoms relative to the enrollment visit on Day 5.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 420 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Diagnostic
Official Title: Targeted Reduction of Antibiotics Using Procalcitonin in a Multi-center, Randomized, Double-Blinded, Placebo-Controlled Non-Inferiority Study of Azithromycin Treatment in Outpatient Adults With Suspect Lower Respiratory Tract Infection (LRTI) and a Procalcitonin (PCT) Level of < /= 0.25 ng/mL (TRAP-LRTI)
Actual Study Start Date : December 8, 2017
Estimated Primary Completion Date : December 29, 2019
Estimated Study Completion Date : February 4, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics

Arm Intervention/treatment
Experimental: Azithromycin
210 subject to receive Azithromycin 500 mg as a single dose on Day 1, followed by Azithromycin 250 mg once daily Day 2 through Day 5
Drug: Azithromycin
Azithromycin is an azalide antibiotic and is derived from erythromycin used to treat many different types of infections caused by bacteria, such as respiratory infections.

Device: VIDAS B.R.A.H.M.S Procalcitonin Test (PCT)
The VIDAS B.R.A.H.M.S PCT is an automated test for use on the VIDAS instruments for the determination of human procalcitonin in human serum or plasma using the Enzyme-Linked Fluorescent Assay (ELFA) technique.

Placebo Comparator: Placebo
210 subject to receive 2 capsules of placebo as a single dose on Day 1, followed by 1 capsule of placebo once daily Day 2 through Day 5
Other: Placebo
Placebo will be a matching capsule the same size, weight, and color as the capsules containing Azithromycin tablets

Device: VIDAS B.R.A.H.M.S Procalcitonin Test (PCT)
The VIDAS B.R.A.H.M.S PCT is an automated test for use on the VIDAS instruments for the determination of human procalcitonin in human serum or plasma using the Enzyme-Linked Fluorescent Assay (ELFA) technique.




Primary Outcome Measures :
  1. Clinical improvement defined as: improvement in > /= 2 symptoms or 1 symptom and 1 vital sign abnormality; no deterioration in symptom or new vital sign abnormality; no fever; no outpatient visits or hospitalization for persistent/worsening LRTI [ Time Frame: Day 5 ]

Secondary Outcome Measures :
  1. Composite overall Desirability Of Outcome Ranking (DOOR) assessed employing a superiority analysis using the "Response Adjusted for Days of Antibiotic Risk (RADAR)" approach [ Time Frame: Day 5 ]
  2. Proportion of subjects reporting > /= 1 hospitalization or visits to an ED, outpatient clinic, or urgent care center (after randomization) for worsening or persistent LRTI in each treatment group [ Time Frame: From Day 1 through Day 5 ]
  3. Proportion of subjects reporting solicited adverse events in each treatment group [ Time Frame: From Day 1 through Day 5 ]
  4. Proportion of subjects with one or more unplanned return visits to a physician's office or urgent care for persistent or worsening LRTI in each treatment group [ Time Frame: From Day 1 through Day 28 ]
  5. Quantification of all antibiotic use in each treatment group [ Time Frame: From Day 1 through Day 28 ]
  6. The proportion of subjects exhibiting improvement in at least one presenting sign or symptom in each treatment group [ Time Frame: Day 11 ]
  7. The proportion of subjects exhibiting improvement in at least one presenting sign or symptom in each treatment group [ Time Frame: Day 28 ]
  8. The proportion of subjects exhibiting improvement in at least one presenting sign or symptom in each treatment group [ Time Frame: Day 5 ]
  9. The proportion of subjects exhibiting worsening or deterioration in at least one or more symptoms in each treatment group [ Time Frame: Day 5 ]
  10. The proportion of subjects with > /= 1 emergency department visits for persistent or worsening LRTI in each treatment group [ Time Frame: From Day 1 through Day 28 ]
  11. The proportion of subjects with > /= 1 hospitalizations (if not hospitalized at enrollment) for persistent or worsening LRTI in each treatment group [ Time Frame: From Day 1 through Day 28 ]
  12. The proportion of subjects with a new occurrence of a vital sign abnormality in each treatment group [ Time Frame: Day 5 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Clinician suspected LRTI* based on the presence of at least two qualifying symptoms** OR one qualifying symptom and at least one qualifying vital sign.***

    *LRTI will include acute bronchitis, tracheitis, tracheobronchitis, asthma exacerbation, and acute exacerbation of COPD but does not include known pneumonia.

    **New cough, worsening of chronic cough, new sputum production, increased volume or purulence of chronic sputum production, chest pain, and difficulty breathing

    ***Fever (Provider or patient-measured temperature =37.8°C (100.0°F) or patient-reported feverishness), tachycardia of =90 beats/minute, tachypnea of more than 20 breaths/minute

  2. Males and females age > /=18 years old.
  3. Presentation > /=24 hours and < /= 28 days after the onset of at least one qualifying symptom related to the acute episode of illness.
  4. Ability to understand study procedures and willing and able to comply with all required procedures and visits for the entire length of study.
  5. Provide written informed consent before initiation of any study procedures.

Exclusion Criteria:

  1. Hospitalized prior to screening and enrollment. Subjects enrolled in clinic or ED setting and then hospitalized during the same clinical encounter may be included.
  2. Chronic pulmonary conditions at the investigator's discretion *

    *As defined by the following:

    • Noninvasive ventilation use for any indication other than obstructive sleep apnea
    • Long-term invasive mechanical ventilation for any indication
    • Known diagnosis of cystic fibrosis or chronic bronchiectasis.
  3. Pulse oximetry reading =90% at baseline or during the enrollment visit but prior to randomization, based on clinically obtained values.
  4. Receipt of an investigational product within 30 days prior to Day 1 or plans to potentially start any investigational product within 30 days after the subject's anticipated study completion.
  5. Current enrollment in another clinical trial of an investigational agent
  6. Known or suspected infection at any other anatomic site requiring antibacterial therapy.
  7. Immunosuppression.*

    *Includes:

    • HIV infection with CD4<200 based on last known measurement or patient-reported value
    • History of hematologic malignancies
    • Receipt of chemotherapy within the previous 6 months or anticipated receipt of chemotherapy during the study period (1 month)
    • Known to have an absolute neutrophil count of <500 cells/mL or an expectation of an absolute neutrophil count of <500 cells/mL during course of the study
    • Current systemic corticosteroid use (equivalent of 20mg prednisone per day for > /= 2 weeks within the last month),
    • Non-steroid immunosuppressive or biologic therapy for transplant, rheumatologic conditions, or other conditions within the last month, regardless of route of administration.
  8. Contraindication to the use of macrolides including history of allergy or intolerance to macrolides or known prolonged QTc interval (> 500msec)
  9. Any condition that in the judgment of the referring provider or site investigator precludes participation because it could affect subject safety or ability of subject to participate in this trial.
  10. Prior use of azithromycin in the past two weeks.
  11. Use of any systemic antibiotic in the previous 24 hours.
  12. Previous randomization in this trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03341273


Contacts
Contact: Ephraim Tsalik e.t@duke.edu

Locations
United States, Georgia
Emory Vaccine Center - The Hope Clinic Recruiting
Atlanta, Georgia, United States, 30332
Atlanta VA Medical Center - Infectious Diseases Clinic Recruiting
Decatur, Georgia, United States, 30033
United States, North Carolina
Durham VA Medical Center Recruiting
Durham, North Carolina, United States, 27705-3875
Duke Human Vaccine Institute - Duke Clinical Vaccine Unit Recruiting
Durham, North Carolina, United States, 27708
United States, Texas
Texas Medical Center - Michael E. DeBakey Veterans Affairs Recruiting
Houston, Texas, United States, 77030-4211
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03341273     History of Changes
Other Study ID Numbers: 15-0020
HHSN272201300015I
First Posted: November 14, 2017    Key Record Dates
Last Update Posted: April 13, 2018
Last Verified: November 5, 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Antibiotic Therapy
Lower Respiratory Tract Infection
Procalcitonin

Additional relevant MeSH terms:
Infection
Communicable Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Anti-Bacterial Agents
Antibiotics, Antitubercular
Calcitonin
Anti-Infective Agents
Antitubercular Agents
Bone Density Conservation Agents
Physiological Effects of Drugs