Lower Respiratory Tract InfectionNCT03341273
Placebo-Controlled Trial of Antibiotic Therapy in Adults With Suspect Lower Respiratory Tract Infection (LRTI) and a Procalcitonin Level
A study testing Azithromycin and VIDAS B.R.A.H.M.S Procalcitonin Test (PCT) in people with Lower Respiratory Tract Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Lower Respiratory Tract Infection
- What is being tested?
- Azithromycin and VIDAS B.R.A.H.M.S Procalcitonin Test (PCT)
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 514 participants
- Where
- 5 sitesUnited States
- Study dates
- 8 Dec 2017to 15 Aug 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 22Show fewer
- 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
- Current systemic corticosteroid use (equivalent of 20mg prednisone per day for > / = 2 weeks within the last month)
- Systemic non-steroid immunosuppressive or biologic therapy for transplant, rheumatologic conditions, or other conditions within the last month. Biologics used specifically for control of moderate to severe asthma, including anti-IgE monoclonal antibody therapy (Xolair) or IL-5 monoclonal antibodies (Mepolizumab and Reslizumab) are allowed
- Contraindication to the use of azithromycin including history of allergy or intolerance to azithromycin or known prolonged QTc interval (> 500 msec).
- 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.
- Prior use of azithromycin in the past two weeks.
- Use of any systemic antibiotic in the previous 24 hours.
- Previous randomization in this trial.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
The Hope Clinic of Emory University
Atlanta, Georgia, 30332
Atlanta VA Medical Center - Infectious Diseases Clinic
Decatur, Georgia, 30033
Durham VA Medical Center
Durham, North Carolina, 27705-3875
Duke Vaccine and Trials Unit
Durham, North Carolina, 27708
Texas Medical Center - Michael E. DeBakey Veterans Affairs
Houston, Texas, 77030-4211
About this study
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)
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.
Read the 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 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. The secondary objectives are to compare:1) groups receiving azithromycin versus placebo with regard to all antibiotic use by Days 11 and 28; 2) groups receiving azithromycin versus placebo with regard to return visits to a physician's office or urgent care by Days 11 and 28; 3) groups receiving azithromycin versus placebo with regard to emergency department visits by Days 11 and 28; 4) groups receiving azithromycin versus placebo with regard to hospitalization by Days 11 and 28 if not hospitalized at the enrollment and randomization visit; 5) groups receiving azithromycin versus placebo with regard to improvement in presenting symptoms by Days 11 and 28; 6) the efficacy of azithromycin versus placebo on Day 11 in subjects with suspect LRTI and PCT levels of < / = 0.25 ng/mL at enrollment using a non-inferiority approach; 7) the efficacy of azithromycin versus placebo on Day 28 in subjects with suspect LRTI and PCT levels of < / = 0.25 ng/mL at enrollment using a non-inferiority approach; 8) 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; 9) groups receiving azithromycin versus placebo in regard to solicited events by Day 5; 10) groups receiving azithromycin versus placebo in regard to hospitalization or visits to an Emergency Department (ED), outpatient clinic, or urgent care center for worsening or persistent LRTI after randomization by Day 5; 11) groups receiving azithromycin versus placebo in regard to improvement in vital sign abnormalities or symptoms present at enrollment, on Day 5; 12) 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.
- Conditions
- Lower Respiratory Tract Infection
- Being tested
- Azithromycin, Placebo, VIDAS B.R.A.H.M.S Procalcitonin Test (PCT)
- Keywords
- Antibiotic Reduction, Antibiotic Therapy, Azyithromycin, Lower Respiratory Tract Infection, Procalcitonin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzithromycinDrug
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.
PlaceboOther
Placebo will be a matching capsule the same size, weight, and color as the capsules containing Azithromycin tablets.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Other: Placebo; Device: VIDAS B.R.A.H.M.S Procalcitonin Test (PCT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Improvement at Day 5 Visit (D5V)
Clinical improvement at Day 5 Visit is defined as fulfilling all of the following criteria:
- Improvement in at least two symptoms present at enrollment or one symptom and at least one vital sign abnormality present at enrollment
- Absence of deterioration in any qualifying symptom or new vital sign abnormality not present at enrollment
- Absence of fever in the day preceding or at the D5V
- 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
Measured: Day 5 Visit
Secondary outcomes (18)
Clinical Improvement at Day 11 Visit (D11V)
Clinical improvement at Day 11 Visit is defined as fulfilling all of the following criteria:
- Improvement in at least two symptoms present at enrollment or one symptom and at least one vital sign abnormality present at enrollment
- Absence of deterioration in any qualifying symptom or new vital sign abnormality not present at enrollment
- Absence of fever in the day preceding or at the D11V
- No medically attended visit to an ambulatory medical facility or hospitalization for persistent or worsening LRTI at any time after randomization The ITT population includes all participants with PCT = 0.25 ng/mL who were randomized to receive study product.
Measured: Day 11 Visit
Clinical Improvement at Day 28 Visit (D28V)
Clinical improvement at Day 28 Visit is defined as fulfilling all of the following criteria:
- Improvement in at least two symptoms present at enrollment or one symptom and at least one vital sign abnormality present at enrollment
- Absence of deterioration in any qualifying symptom or new vital sign abnormality not present at enrollment
- Absence of fever in the day preceding or at the D11V
- No medically attended visit to an ambulatory medical facility or hospitalization for persistent or worsening LRTI at any time after randomization
Measured: 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
DOOR is a composite endpoint created using clinical outcomes from Day 1 through Day 5 Visit. It is based on adequate clinical improvement at Day 5 Visit and solicited events from Day 1 through Day 5 Visit.
When comparing two participants with different ordinal clinical outcomes (OCOs), the participant with a better OCO receives a higher DOOR rank. When comparing two participants with the same OCOs, the participant with fewer days of antibiotic use receives a higher DOOR rank.
Measured: Day 5 Visit
Number of Participants Exhibiting Improvement in One or More LRTI Symptoms or Fever at Day 11 Visit
Improvement in LRTI symptoms was defined as presence of at least one-step improvement in the symptom present at baseline. For fever, improvement was defined as changing from presence of fever at baseline to absence of fever at Day 11 Visit.
Measured: Day 11 Visit
Number of Participants Exhibiting Improvement in One or More LRTI Symptoms or Fever at Day 28 Visit
Improvement in LRTI symptoms was defined as presence of at least one-step improvement in the symptom present at baseline. For fever, improvement was defined as changing from presence of fever at baseline to absence of fever at Day 28 Visit.
Measured: Day 28 Visit
Number of Participants Exhibiting Improvement in at Least Two Presenting Signs or Symptoms at Day 5 Visit
Improvement in LRTI symptoms was defined as presence of at least one-step improvement in at least two symptoms present at baseline for participants who qualified based on two symptoms or improvement in one LRTI symptom present at baseline and normalization of one abnormal vital sign at Day 5 Visit for participants who qualified based on one symptom and one vital sign abnormality.
Measured: Day 5 Visit
Number of Participants Exhibiting Worsening or Deterioration in One or More Symptoms at Day 5 Visit
Clinical deterioration at D5V is defined as at least one-step deterioration (worsening from mild to moderate for example) in any qualifying symptoms or presence of a new vital abnormality at D5V not present at enrollment.
Measured: Day 5 Visit
Number of Participants Reporting One or More Hospitalization or Visits to an Emergency Department (ED), Outpatient Clinic, or Urgent Care Center (After Randomization) for Worsening or Persistent Lower Respiratory Tract Infection
This table summarizes the number and percentage of participants reporting any medically attended visits any time after randomization. Note that receipt of a non-study antibiotic after study Day 5 Visit will was not regarded as satisfying this definition if it is related to a new non-respiratory process that is unrelated to the prior diagnosis of LRTI.
Measured: Day 1 through Day 5 Visit
Number of Participants Reporting Solicited Adverse Events From Day 1 Through Day 5 Visit
This table summarizes the number and percentage of participants experiencing any solicited events of mild, moderate or severe severity from Day 1 to Day 5 Visit.
Measured: Day 1 through Day 5 Visit
Number of Participants With One or More Emergency Department Visits for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 11 Visit
This table summarizes the number of participants with one or more Emergency Department Visits for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) from Day 1 through Day 11 Visit.
Measured: Day 1 through Day 11
Number of Participants With One or More Emergency Department Visits for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 28 Visit
This table summarizes the number of participants with one or more Emergency Department Visits for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) in Azithromycin Group from Day 1 through Day 28 Visit.
Measured: Day 1 through Day 28 Visit
Number of Participants With One or More Hospitalizations (if Not Hospitalized at Enrollment) for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 11 Visit
This table summarizes the number of participants with one or more hospitalizations for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) from Day 1 through Day 11 Visit.
Measured: Day 1 through Day 11 Visit
Number of Participants With One or More Hospitalizations (if Not Hospitalized at Enrollment) for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 28 Visit
This table summarizes the number of participants with one or more hospitalizations for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) from Day 1 through Day 28 Visit.
Measured: Day 1 through Day 28 Visit
Number of Participants With One or More Unplanned Return to a Physician's Office or Urgent Care for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 11 Visit
This table summarizes the number of participants with one or more unplanned Return to a Physician's Office or Urgent Care for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) from Day 1 through Day 11 Visit.
Measured: Day 1 through Day 11 Visit
Number of Participants With One or More Unplanned Return to a Physician's Office or Urgent Care for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 28 Visit
This table summarizes the number of participants with one or more unplanned Return to a Physician's Office or Urgent Care for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) from Day 1 through Day 28 Visit.
Measured: Day 1 through Day 28 Visit
Number of Participants With a New Occurrence of a Vital Sign Abnormality at Day 5 Visit
This table summarizes the number and percentage of participants experiencing new vital signs abnormalities at Day 5 Visit that were not present at baseline.
Measured: Day 5 Visit
Quantification of All Antibiotic Use From Day 1 Through Day 11 Visit
The table summarizes the mean number of days of antibiotic use including study and non-study antibiotics for participants from Day 1 through Day 11 Visit.
Measured: Day 1 through Day 11 Visit
Quantification of All Antibiotic Use From Day 1 Through Day 28 Visit
The table summarizes the mean number of days of antibiotic use including study and non-study antibiotics for participants from Day 1 through Day 28 Visit.
Measured: Day 1 through Day 28 Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2017
- Study start8 Dec 2017
- Primary completion30 Mar 2020
- Study completion15 Aug 2020
Why it stopped: Due to covid
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lower Respiratory Tract InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 514 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03341273
- Sponsor's protocol ID
- 15-0020
- Other IDs
- HHSN272201300015I
- Status last verified
- 12 Mar 2020
- First submitted
- 9 Nov 2017
- Last updated
- 28 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
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.
PubMed 36525985
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03341273
- Acronym / sponsor ID
- 15-0020
- Conditions
- Lower Respiratory Tract Infection
- Keywords
- Antibiotic Reduction, Antibiotic Therapy, Azyithromycin, Lower Respiratory Tract Infection, Procalcitonin
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to covid
- Enrolment
- 514 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 8 Dec 2017 (actual)
- Primary completion
- 30 Mar 2020 (actual)
- Study completion
- 15 Aug 2020 (actual)
- First posted
- 14 Nov 2017 (actual)
- Results
- Posted 24 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 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. The secondary objectives are to compare:1) groups receiving azithromycin versus placebo with regard to all antibiotic use by Days 11 and 28; 2) groups receiving azithromycin versus placebo with regard to return visits to a physician's office or urgent care by Days 11 and 28; 3) groups receiving azithromycin versus placebo with regard to emergency department visits by Days 11 and 28; 4) groups receiving azithromycin versus placebo with regard to hospitalization by Days 11 and 28 if not hospitalized at the enrollment and randomization visit; 5) groups receiving azithromycin versus placebo with regard to improvement in presenting symptoms by Days 11 and 28; 6) the efficacy of azithromycin versus placebo on Day 11 in subjects with suspect LRTI and PCT levels of < / = 0.25 ng/mL at enrollment using a non-inferiority approach; 7) the efficacy of azithromycin versus placebo on Day 28 in subjects with suspect LRTI and PCT levels of < / = 0.25 ng/mL at enrollment using a non-inferiority approach; 8) 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; 9) groups receiving azithromycin versus placebo in regard to solicited events by Day 5; 10) groups receiving azithromycin versus placebo in regard to hospitalization or visits to an Emergency Department (ED), outpatient clinic, or urgent care center for worsening or persistent LRTI after randomization by Day 5; 11) groups receiving azithromycin versus placebo in regard to improvement in vital sign abnormalities or symptoms present at enrollment, on Day 5; 12) 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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Azithromycin | Experimental | Drug: Azithromycin, Device: VIDAS B.R.A.H.M.S Procalcitonin Test (PCT)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 |
| Placebo | Placebo comparator | Other: Placebo, Device: VIDAS B.R.A.H.M.S Procalcitonin Test (PCT)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 |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (22 listed)
- 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*.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzithromycinAzithromycin is an azalide antibiotic and is derived from erythromycin used to treat many different types of infections caused by bacteria, such as respiratory infections. | Drug | Azithromycin |
| PlaceboPlacebo will be a matching capsule the same size, weight, and color as the capsules containing Azithromycin tablets. | Other | Placebo |
| 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. | Device | Azithromycin, Placebo |
Primary outcome
Clinical Improvement at Day 5 Visit (D5V)
Time frame: Day 5 Visit
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
18 secondary outcomes
Clinical Improvement at Day 11 Visit (D11V)
Time frame: Day 11 Visit
Clinical Improvement at Day 28 Visit (D28V)
Time frame: 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
Time frame: Day 5 Visit
Number of Participants Exhibiting Improvement in One or More LRTI Symptoms or Fever at Day 11 Visit
Time frame: Day 11 Visit
Number of Participants Exhibiting Improvement in One or More LRTI Symptoms or Fever at Day 28 Visit
Time frame: Day 28 Visit
Number of Participants Exhibiting Improvement in at Least Two Presenting Signs or Symptoms at Day 5 Visit
Time frame: Day 5 Visit
Number of Participants Exhibiting Worsening or Deterioration in One or More Symptoms at Day 5 Visit
Time frame: Day 5 Visit
Number of Participants Reporting One or More Hospitalization or Visits to an Emergency Department (ED), Outpatient Clinic, or Urgent Care Center (After Randomization) for Worsening or Persistent Lower Respiratory Tract Infection
Time frame: Day 1 through Day 5 Visit
Number of Participants Reporting Solicited Adverse Events From Day 1 Through Day 5 Visit
Time frame: Day 1 through Day 5 Visit
Number of Participants With One or More Emergency Department Visits for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 11 Visit
Time frame: Day 1 through Day 11
Number of Participants With One or More Emergency Department Visits for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 28 Visit
Time frame: Day 1 through Day 28 Visit
Number of Participants With One or More Hospitalizations (if Not Hospitalized at Enrollment) for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 11 Visit
Time frame: Day 1 through Day 11 Visit
Number of Participants With One or More Hospitalizations (if Not Hospitalized at Enrollment) for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 28 Visit
Time frame: Day 1 through Day 28 Visit
Number of Participants With One or More Unplanned Return to a Physician's Office or Urgent Care for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 11 Visit
Time frame: Day 1 through Day 11 Visit
Number of Participants With One or More Unplanned Return to a Physician's Office or Urgent Care for Persistent or Worsening Lower Respiratory Tract Infection (LRTI) by Day 28 Visit
Time frame: Day 1 through Day 28 Visit
Number of Participants With a New Occurrence of a Vital Sign Abnormality at Day 5 Visit
Time frame: Day 5 Visit
Quantification of All Antibiotic Use From Day 1 Through Day 11 Visit
Time frame: Day 1 through Day 11 Visit
Quantification of All Antibiotic Use From Day 1 Through Day 28 Visit
Time frame: Day 1 through Day 28 Visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36525985Tsalik 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Azithromycin and VIDAS B.R.A.H.M.S Procalcitonin Test (PCT) in people with Lower Respiratory Tract Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Improvement at Day 5 Visit (D5V) (time frame: Day 5 Visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03341273, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2023.