APLAUD Trial (Antibiotics vs PLacebo for Acute Uncomplicated Diverticulitis)

April 15, 2026 updated by: Alexander Hawkins, Vanderbilt University Medical Center

Comparing Placebo Versus Antibiotics for Acute Uncomplicated Diverticulitis

The goal of this clinical trial is to determine whether antibiotics improve recovery from acute uncomplicated diverticulitis (AUD) in racially and ethnically diverse United States clinical practice. The main questions it seeks to answer are:

  • What is the feasibility for completing a subsequent definitive efficacy trial of antibiotics vs. placebo to treat AUD?
  • What are the needs for successful recruitment of racial and ethnic subgroups?
  • What are the effects of a placebo compared to antibiotics for AUD on a range of key patient-centric efficacy and safety endpoints?
  • How do such effects differ by race and ethnicity? Researchers will compare a placebo to antibiotics to see if AUD can be treated without using antibiotics.

Participants will:

  • Take two antibiotics or a matching placebo every day for 10 days
  • Receive analgesia, gastric protection, diet modifications, and a follow-up
  • Submit daily photos of pills to the study team to verify adherence

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37235
        • Vanderbilt University Medical Center Emergency Department
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients presenting to the emergency department with left-sided uncomplicated diverticulitis
  • Radiologic score (moderate diverticulitis per Ambrosetti classification)
  • Age 18-90
  • Access to a smartphone with internet access.

Exclusion Criteria:

  • Complicated diverticulitis (abscess, free air, peritonitis)- severe diverticulitis by Ambrosetti classification
  • Diverticulitis other than left colon
  • Contraindication to use of study medication (ie advanced renal failure or allergy to all antibiotics used in the study)
  • Concurrent cancer diagnosis
  • Concurrent IBD Diagnosis
  • Any other disease process with life expectancy < 6 months
  • Concurrent chronic pain diagnosis.
  • Women in pregnancy or breastfeeding
  • Antibiotic treatment for any reason in the last 3 weeks
  • Diagnosis of prior episode of acute diverticulitis in the past 3 months
  • Significant comorbidities: diabetes mellitus with organic involvement (retinopathy, angiopathy, nephropathy), emergency assistance for a cardiogenic event in the last 3 months (acute myocardial infarction, angina, heart failure), decompensation of chronic liver disease in the last 3 months (Child ≥ B) and end-stage renal disease.
  • Immunodepression: the absence, and immunodepression is the presence, of any of the following: active neoplastic disease, hematologic malignancy, human immunodeficiency virus long-term corticosteroid treatment, immunosuppressant therapy (20mg pred (or equivalent) for >2 weeks), transplant, splenectomy and genetic immunodeficiency
  • Previous colectomy
  • Patients with dementia, memory disorders or other cognitive impairment that would impact their ability to provide informed consent or otherwise participate in the trial

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Placebo
A placebo matching the antibiotic arm's treatment regimen will be administered for 10 days
Drug: Placebo
A placebo matching the antibiotic arm's treatment regimen will be administered for 10 days
Active Comparator: Antibiotic
The primary antibiotic choice will be amoxicillin-clavulanate (1 tablet [875 mg amoxicillin; 125 mg clavulanic acid] every 8 hours). If the subject has an allergy or contraindication to the primary antibiotic, we will administer cefuroxime [500 mg] every 12 hours plus metronidazole [500 mg] every 12 hours.
Drug: Amoxicillin-Clavulanate 875 Mg-125 Mg Oral Tablet
amoxicillin-clavulanate:1 tablet [875 mg amoxicillin; 125 mg clavulanic acid] every 8 hours
Drug: Metronidazole
metronidazole: 500 mg every 12 hours
Drug: Cefuroxime
cefuroxime: 500 mg every 12 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Recruitment Rate
Time Frame: From enrollment through study completion, an average of 2 years.
Patients recruited per week
From enrollment through study completion, an average of 2 years.
Adherence
Time Frame: From enrollment through study completion, an average of 2 years
Percent of patients completing the course of antibiotics/placebo
From enrollment through study completion, an average of 2 years
Data completeness
Time Frame: From enrollment through study completion, an average of 2 years
Percentage of participants for whom a complete data set was collected
From enrollment through study completion, an average of 2 years
Retention
Time Frame: From enrollment through study completion, an average of 2 years
Percentage of patients completing all study activities
From enrollment through study completion, an average of 2 years
Acceptability
Time Frame: Collected at 14 days and 6 months
Measured by the Acceptability of Intervention Measure (AIM). Four-question survey with scores ranging from 4 (least acceptable) to 20 (most acceptable).
Collected at 14 days and 6 months
Cross over
Time Frame: From enrollment through study completion, an average of 2 years
Defined as the number of placebo subjects that ended up being treated with antibiotics
From enrollment through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Barratt Simplified Measure of Social Status (BSMSS)
Time Frame: Collected at the time of enrollment
BSMSS provides an education, occupation, and overall proxy score for socioeconomic status. Scored on a scale of 8-66, with higher scores indicating higher socioeconomic status.
Collected at the time of enrollment
Brief Health Literacy Scale (BHLS)
Time Frame: Collected at enrollment
3-item questionnaire, scored on a scale of 1-5 with 5 being the highest degree of health literacy
Collected at enrollment
Patient-Reported Outcomes Measurement Information System-10 (PROMIS-10)
Time Frame: Collected at the time of enrollment, 30 days, and 6 months
The PROMIS-10 assesses an individual's mental health (four items) and physical health (four items) domains. The total raw scores are translated into standardized T-scores with a mean of 50 and a SD of 10
Collected at the time of enrollment, 30 days, and 6 months
Diverticulitis quality of life (DV-QOL) instrument
Time Frame: Collected at enrollment, then 14 and 30 days into the study.
This instrument was designed and validated to measure patient-reported burden of diverticular disease. It is a 17-question survey of patient-reported burden of disease focused on those with uncomplicated diverticular disease. The survey has raw scores 0-68, with higher scores indicating greater impact of diverticulitis on the patient's quality of life. The raw scores are scaled to a 10-point scale.
Collected at enrollment, then 14 and 30 days into the study.
Patient-Reported Outcomes Measurement Information System, Gastrointestinal
Time Frame: Collected at enrollment and 14 days into study
5 item survey that assesses abdominal pain, scored 5-25 with higher scores indicating more severe abdominal pain
Collected at enrollment and 14 days into study
Time to normalization of abdominal pain intensity
Time Frame: Collected at enrollment, daily for 30 days, and at 6 months
11-point numerical rating scale (NRS) from 0 (no pain) to 10 (worst possible pain) that asks subjects daily to rate their worst abdominal pain over the past 24-hours
Collected at enrollment, daily for 30 days, and at 6 months
Rate of Progression to Complicated Diverticulitis
Time Frame: Collected at enrollment, 14 days, 30 days, and 6 months
Captured via review of the EMR and any follow up CT scans
Collected at enrollment, 14 days, 30 days, and 6 months
Rate of persistent diverticulitis at 30 days
Time Frame: Collected 30 days from enrollment
DV-QOL scores below the patient acceptable symptom state threshold of 3.2/10
Collected 30 days from enrollment
Rate of diverticulitis-related hospitalization, percutaneous drainage and colectomy
Time Frame: From enrollment through study completion, an average of 2 years
Collected from EMR and patient queries
From enrollment through study completion, an average of 2 years
Mortality
Time Frame: From enrollment through study completion, an average of 2 years
Obtained from Social Security Administration Death Master File
From enrollment through study completion, an average of 2 years
Adverse Drug Events
Time Frame: From enrollment through study completion, an average of 2 years
Including, but not limited to rash, diarrhea, urticaria and anaphylaxis will be captured using self-reported surveys with review of the EMR
From enrollment through study completion, an average of 2 years
Return to normal activity
Time Frame: From enrollment through study completion, an average of 2 years

For subjects who currently are employed, the researchers will ask baseline information about past-month work absenteeism (missed work due to health) and presenteeism (impaired work due to health). The subject will complete the validated Work Productivity and Activity Impairment questionnaire. At each follow up period, the researchers will repeat these measures and inquire if they had suffered an adverse work event (firing, demotion) and if they have had to go on any leave.

This is a 6- item instrument on a visual analog scale of 0-10. Scores for each item are multiplied by 100 to calculate percentages. The WPAI calculates percentage impairment (maximum 100%) with higher numbers representing greater work impairment.
From enrollment through study completion, an average of 2 years
Recurrence
Time Frame: From 8 weeks into the study through study completion, an average of 2 years
CT-proven acute diverticulitis after complete resolution of symptoms more than 2 months after initial evaluation in the ED. This will be captured by review of the EMR and direct patient query
From 8 weeks into the study through study completion, an average of 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University Medical Center

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2026

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

March 11, 2026

First Submitted That Met QC Criteria

March 18, 2026

First Posted (Actual)

March 25, 2026

Study Record Updates

Last Update Posted (Actual)

April 21, 2026

Last Update Submitted That Met QC Criteria

April 15, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 251398
  • 1R01DK141523-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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