APLAUD Trial (Antibiotics vs PLacebo for Acute Uncomplicated Diverticulitis)

Phase 2Not Yet RecruitingNCT07492134

Vanderbilt University Medical Center100 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

100

Conditions

Acute Uncomplicated Diverticulitis

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Recruitment Rate

Patients recruited per week

Time frame: From enrollment through study completion, an average of 2 years.

Adherence

Percent of patients completing the course of antibiotics/placebo

Time frame: From enrollment through study completion, an average of 2 years

Data completeness

Percentage of participants for whom a complete data set was collected

Time frame: From enrollment through study completion, an average of 2 years

Retention

Percentage of patients completing all study activities

Time frame: From enrollment through study completion, an average of 2 years

Acceptability

Measured by the Acceptability of Intervention Measure (AIM). Four-question survey with scores ranging from 4 (least acceptable) to 20 (most acceptable).

Time frame: Collected at 14 days and 6 months

Cross over

Defined as the number of placebo subjects that ended up being treated with antibiotics

Time frame: From enrollment through study completion, an average of 2 years

Secondary Outcomes

Barratt Simplified Measure of Social Status (BSMSS)

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.

Time frame: Collected at the time of enrollment

Brief Health Literacy Scale (BHLS)

3-item questionnaire, scored on a scale of 1-5 with 5 being the highest degree of health literacy

Time frame: Collected at enrollment

Patient-Reported Outcomes Measurement Information System-10 (PROMIS-10)

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

Time frame: Collected at the time of enrollment, 30 days, and 6 months

Diverticulitis quality of life (DV-QOL) instrument

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.

Time frame: Collected at enrollment, then 14 and 30 days into the study.

Patient-Reported Outcomes Measurement Information System, Gastrointestinal

5 item survey that assesses abdominal pain, scored 5-25 with higher scores indicating more severe abdominal pain

Time frame: Collected at enrollment and 14 days into study

Time to normalization of abdominal pain intensity

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

Time frame: Collected at enrollment, daily for 30 days, and at 6 months

Rate of Progression to Complicated Diverticulitis

Captured via review of the EMR and any follow up CT scans

Time frame: Collected at enrollment, 14 days, 30 days, and 6 months

Rate of persistent diverticulitis at 30 days

DV-QOL scores below the patient acceptable symptom state threshold of 3.2/10

Time frame: Collected 30 days from enrollment

Rate of diverticulitis-related hospitalization, percutaneous drainage and colectomy

Collected from EMR and patient queries

Time frame: From enrollment through study completion, an average of 2 years

Mortality

Obtained from Social Security Administration Death Master File

Time frame: From enrollment through study completion, an average of 2 years

Adverse Drug Events

Including, but not limited to rash, diarrhea, urticaria and anaphylaxis will be captured using self-reported surveys with review of the EMR

Time frame: From enrollment through study completion, an average of 2 years

Return to normal activity

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.

Time frame: From enrollment through study completion, an average of 2 years

Recurrence

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

Time frame: From 8 weeks into the study through study completion, an average of 2 years

APLAUD Trial (Antibiotics vs PLacebo for Acute Uncomplicated Diverticulitis)

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes