CClinicalTrials.gg
RecruitingNCT07164131AD-CAPUpdated Sep 24, 2026

Azithromycin Versus Doxycycline in Hospitalized Adult Patients With Community Acquired Pneumonia Treated With Beta-lactams

A Phase 4 interventional study of Doxycycline and Azithromycin in Community-acquired Pneumonia, sponsored by Mayo Clinic. Recruiting at 5 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-24.

Sponsored by Mayo Clinic · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
1,120
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to compare effectiveness and safety of Azithromycin versus Doxycycline in adult patients hospitalized with community acquired pneumonia (CAP) treated with Beta-lactams.

02

Conditions studied

  • Community-acquired Pneumonia

Keywords

  • Azithromycin
  • Doxycycline
  • hospitalized
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • All adult patients (>18 years old) admitted with CAP and receiving a beta-lactam antibiotic plus a form of atypical coverage (azithromycin or doxycycline) in the ED within 12 hours of admission.

Exclusion criteria

Exclusion Criteria:

  • High clinical suspicion for Legionella pneumonia
  • Allergy or contraindication to the use of either azithromycin or doxycycline (usual clinical practice)
  • Antibiotics not for CAP
  • Pregnant women (based on clinical assessment as part of standard of care)
  • Severe CAP as defined by the ATS/IDSA criteria
  • Corrected QT prolongation (> 450 ms in men and > 460 ms in women)
  • Incarcerated individuals (prisoner)
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
1,120 participants (estimated)

Study arms

  • Active comparator
    Doxycycline group

    Subjects hospitalized for community acquired pneumonia will receive standard of care treatment with Doxycycline

    Drug: Doxycycline

  • Active comparator
    Azithromycin group

    Subjects hospitalized for community acquired pneumonia will receive standard of care treatment with Azithromycin

    Drug: Azithromycin

Interventions

  • DrugDoxycycline

    Subjects will receive Doxycycline (orally or intravenously) in combination with beta-lactam therapy within 12 hours of hospital admission. Treatment duration will be determined by treating clinician (5-7 days per guidelines).

  • DrugAzithromycin

    Subjects will receive Azithromycin (orally or intravenously) in combination with beta-lactam therapy within 12 hours of hospital admission. Treatment duration will be determined by treating clinician (5-7 days per guidelines).

05

What researchers measure

Primary outcomes

  1. Days alive and out of hospital

    Days alive spent outside of the hospital, within 28 days of randomization

    Time frame: 28 days

Secondary outcomes

  1. Oxygen-free days

    Number of days subject does not require new supplemental oxygen use. Oxygen-free days will be set as 0 for patients who died during the stay or had a length of stay of ≥28 days

    Time frame: 28 days

  2. Need for advanced respiratory support or in-hospital mortality

    Defined as a composite of need for advanced respiratory support or mortality during hospitalization. Need for advanced respiratory support would include need for high flow nasal cannula, non-invasive positive pressure ventilation, and invasive ventilation in patients not requiring this at baseline.

    Time frame: 28 days

  3. Need for Advanced Respiratory Support

    Need for advanced respiratory support including invasive mechanical ventilation, non-invasive mechanical ventilation, high flow nasal cannula,

    Time frame: 28 days

  4. In-Hospital Mortality

    Mortality during hospitalization

    Time frame: 28 days

  5. Ordinal clinical status scale

    Change from baseline on an ordinal clinical status scale from hospitalized, not requiring supplemental oxygen, to death

    Time frame: 28 days

  6. 60-day Mortality

    Defined as mortality at 60 days after discharge

    Time frame: 60 days post discharge

  7. 180-day mortality

    Defined as mortality at 180 days after discharge

    Time frame: 180 days

Other outcomes

  1. Incident Clostridioides difficile infection

    Positive stool antigen test, will only be assessed when testing is ordered as part of routine clinical care

    Time frame: 28 days

  2. New arrhythmias requiring intervention and/or QT prolongation

    Outcome will only be assessed when an ECG is ordered as part of routine clinical care

    Time frame: 28 days

06

Study locations

1 of 5 sites recruiting
  • Mayo Clinic in Arizona
    Scottsdale, Arizona 85259, United States
    • Cyril Varghese · Principal investigator
    Not yet recruiting
  • Mayo Clinic in Florida
    Jacksonville, Florida 32224, United States
    • Swetha Reddy · Principal investigator
    Not yet recruiting
  • Mayo Clinic Health System-Mankato
    Mankato, Minnesota 56001, United States
    • Mohamad El Labban · Principal investigator
    Not yet recruiting
  • Mayo Clinic in Rochester
    Rochester, Minnesota 55905, United States
    • Amy Amsbaugh · Contact · amsbaugh.amy@mayo.edu · 507-538-7538
    • Yewande Efunpeju Odeyemi · Principal investigator
    Recruiting
  • Mayo Clinic Health System-La Crosse
    La Crosse, Wisconsin 54601, United States
    • Melissa K Myers · Principal investigator
    Not yet recruiting
07

References and documents

Publications

  • Tekin A, Lal A, Brogan A, Bellolio F, O'Horo JC, Yadav H, Schulte P, Gajic O, Barreto EF, Odeyemi YE; Acute Care Clinical Trial Platform Investigators. Azithromycin versus doxycycline in hospitalised adult patients with community-acquired pneumonia treated with beta-lactams: protocol for a pragmatic randomised clinical trial. BMJ Open. 2026 Jul 27;16(7):e118028. doi: 10.1136/bmjopen-2026-118028. PubMed 42509011 ↗

Individual participant data

Plan to share: Yes — De-identified individual participant data and the accompanying data dictionary will be made available in a secure, controlled-access data repository within one year of publication. Statistical code (R scripts) and supporting documentation will be shared via GitHub to enable transparency and reproducibility.

Supporting information: Study protocol, Analytic code

08

Registry details

Key details

Study ID
NCT07164131
Lead sponsor
Mayo Clinic
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Responsible party
Ognjen Gajic (Principal Investigator, Mayo Clinic) — Principal investigator
First posted
Sep 9, 2025
Start date
Sep 15, 2025
Primary completion
Sep 1, 2030 (estimated)
Completion
Sep 1, 2031 (estimated)
Last update
Sep 24, 2026

Study contacts

Amy Amsbaugh, RRT
Contact
amsbaugh.amy@mayo.edu
5075387538
Aysun Tekin, MD, MS
Contact
tekin.aysun@mayo.edu
5072661273
Ognjen Gajic, MD MS
principal investigator · Mayo Clinic
Yewande Odeyemi, MBBS MS
principal investigator · Mayo Clinic

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion