Placebo-Controlled Trial of Antibiotic Therapy in Adults With Suspect Lower Respiratory Tract Infection (LRTI) and a Procalcitonin Level

NCT03341273 | Terminated Results FDA Device

• 2 other identifiers: 15-0020HHSN272201300015I
• Study Type: interventional
• Target: 514
• Locations: 1 country
• Sites: 5

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 Lower Respiratory Tract Infection (LRTI) and a Procalcitonin (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. The enrollment cap will be 840 participants, for the goal of approximately 674 randomized participants who 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.

Conditions

Lower Respiratory Tract Infection

Keywords

Antibiotic Reduction; Antibiotic Therapy; Azyithromycin; Lower Respiratory Tract Infection; Procalcitonin

Outcome Measures

Primary Outcomes (1)

• Clinical Improvement at Day 5 Visit (D5V)

  Clinical improvement at Day 5 Visit is defined as fulfilling all of the following criteria: 1. Improvement in at least two symptoms present at enrollment or one symptom and at least one vital sign abnormality present at enrollment 2. Absence of deterioration in any qualifying symptom or new vital sign abnormality not present at enrollment 3. Absence of fever in the day preceding or at the D5V 4. No medically attended visit to an ambulatory medical facility or hospitalization for persistent or worsening Lower Respiratory Tract Infection (LRTI) at any time after randomization

  Day 5 Visit

Secondary Outcomes (18)

• Clinical Improvement at Day 11 Visit (D11V)

  Day 11 Visit

• Clinical Improvement at Day 28 Visit (D28V)

  Day 28 Visit

• Composite Overall Desirability of Outcome Ranking (DOOR) Assessed Employing a Superiority Analysis Using the "Response Adjusted for Days of Antibiotic Risk (RADAR)" Approach at Day 5 Visit

  Day 5 Visit

• Number of Participants Exhibiting Improvement in One or More LRTI Symptoms or Fever at Day 11 Visit

  Day 11 Visit

• Number of Participants Exhibiting Improvement in One or More LRTI Symptoms or Fever at Day 28 Visit

  Day 28 Visit

Study Arms (2)

Azithromycin

EXPERIMENTAL

500 mg of Azithromycin (2 capsules of 250 mg) administered orally as a single dose on Day 1, followed by 250 mg capsule of Azithromycin administered orally once daily for 4 days (Day 2 through Day 5). N=337

Drug: Azithromycin; Device: VIDAS B.R.A.H.M.S Procalcitonin Test (PCT)

Placebo

PLACEBO COMPARATOR

2 capsules of Azithromycin placebo administered orally as a single dose on Day 1, followed by 1 capsule of Azithromycin placebo administered orally once daily for 4 days (Day 2 through Day 5). N=337

Other: Placebo; Device: VIDAS B.R.A.H.M.S Procalcitonin Test (PCT)

Interventions

Azithromycin DRUG

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.

Azithromycin

Placebo OTHER

Placebo will be a matching capsule the same size, weight, and color as the capsules containing Azithromycin tablets.

Placebo

VIDAS B.R.A.H.M.S Procalcitonin Test (PCT) DEVICE

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.

Azithromycin; Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinician suspected Lower Respiratory Tract Infection (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 Chronic obstructive pulmonary disease (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 degrees Celsius (100.0 degrees Fahrenheit) or patient-reported feverishness), tachycardia of \> / = 90 beats/minute, tachypnea of \> 20 breaths/minute.
• Males and females age \> / = 18 years old.
• Presentation \> / = 24 hours and \< / = 28 days after the onset of at least one qualifying symptom related to the acute episode of illness.
• Ability to understand study procedures and willing and able to comply with all required procedures and visits for the entire length of study.
• Provide written informed consent before initiation of any study procedures.

You may not qualify if:

• Hospitalized prior to screening and enrollment. Subjects enrolled in clinic or Emergency Department (ED) setting and then hospitalized during the same clinical encounter may be included.
• Chronic pulmonary conditions at the investigator's discretion\*.
• \*Such as:
• 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.
• 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.
• Current enrollment in another clinical trial of an investigational agent.
• Known or suspected infection at any other anatomic site requiring antibacterial therapy.
• Immunosuppression\*
• \*Includes:
• Human Immunodeficiency Virus (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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (5)

The Hope Clinic of Emory University

Atlanta, Georgia, 30332, United States

Location

Atlanta VA Medical Center - Infectious Diseases Clinic

Decatur, Georgia, 30033, United States

Location

Durham VA Medical Center

Durham, North Carolina, 27705-3875, United States

Location

Duke Vaccine and Trials Unit

Durham, North Carolina, 27708, United States

Location

Texas Medical Center - Michael E. DeBakey Veterans Affairs

Houston, Texas, 77030-4211, United States

Location

Related Publications (1)

• Tsalik EL, Rouphael NG, Sadikot RT, Rodriguez-Barradas MC, McClain MT, Wilkins DM, Woods CW, Swamy GK, Walter EB, El Sahly HM, Keitel WA, Mulligan MJ, Tuyishimire B, Serti E, Hamasaki T, Evans SR, Ghazaryan V, Lee MS, Lautenbach E; TRAP-LRTI Study Group; Antibacterial Resistance Leadership Group. Efficacy and safety of azithromycin versus placebo to treat lower respiratory tract infections associated with low procalcitonin: a randomised, placebo-controlled, double-blind, non-inferiority trial. Lancet Infect Dis. 2023 Apr;23(4):484-495. doi: 10.1016/S1473-3099(22)00735-6. Epub 2022 Dec 13.

  PMID: 36525985 DERIVED

MeSH Terms

Interventions

Azithromycin

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Ephraim L. Tsalik, MD, MHS, PhD
• Organization: Duke University

e.t@duke.edu

919-684-3114

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2017
• First Posted: November 14, 2017
• Study Start: December 8, 2017
• Primary Completion: March 30, 2020
• Study Completion: August 15, 2020
• Last Updated: June 28, 2023
• Results First Posted: August 24, 2021

Record last verified: 2020-03-12

Locations

US (5)