Non-antibiotic Management in Acute Uncomplicated Diverticulitis (NAMAD)

Non-antibiotic Management in Acute Uncomplicated Diverticulitis: Randomized Open Label-controlled Trial

Diverticulitis is a common condition that causes swelling and pain in part of the colon (the large intestine). Doctors classify it as "mild" when there are no serious complications.

For many years, doctors in the United States have treated mild diverticulitis with antibiotics. New studies from Europe suggest that many people with mild diverticulitis may not need antibiotics and can get better with just pain medicines. But this approach has not been tested in the United States, where antibiotics are still the standard treatment.

The goal of this clinical trial is to find out if people with mild diverticulitis can be safely treated at home without antibiotics. The main questions it aims to answer are:

• Are people treated without antibiotics admitted to the hospital more often than people treated with antibiotics?
• Do people treated without antibiotics have more emergency room visits, worsening of their disease, or need for surgery?

Researchers will compare two groups of people who come to the emergency department with mild diverticulitis to see if treatment without antibiotics is as safe as treatment with antibiotics.

Participants will:

• Be sent home with pain medicines (ibuprofen and acetaminophen) only, or with pain medicines plus an antibiotic taken by mouth for 7 days
• Follow a liquid diet and slowly return to normal food as they feel better
• Come back to clinic for a check-up at 1 to 2 weeks
• Answer phone calls about their health at 4 weeks, 3 months, and 6 months

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Uncomplicated Diverticulitis
• Intervention / Treatment: Drug: Symptomatic treatment (ibuprofen and acetaminophen); Drug: Amoxicillin-clavulanate; Drug: Ciprofloxacin plus metronidazole

Detailed Description

BACKGROUND AND RATIONALE

Current guidelines from the American Gastroenterological Association (AGA) and the American Society of Colon and Rectal Surgeons (ASCRS) recommend selective rather than routine antibiotic use for acute uncomplicated diverticulitis. These recommendations are based primarily on four randomized trials conducted outside the United States: Antibiotic Therapy of Acute Uncomplicated Colonic Diverticulitis study (AVOD, Sweden, 2012 NCT01008488); Diverticulitis: Antibiotics or Close Observation? study (DIABOLO, Netherlands, 2017, NCT01111253); Selective Treatment with Antibiotics for Non-complicated Diverticulitis study (STAND, New Zealand/Australia, 2021, Australian clinical trials registration number: 12615000249550); and the Randomized Clinical Trial to Compare the Treatment of Mild Acute Diverticulitis With or Without Antibiotics (DINAMO) study (Spain, 2021, NCT02785549). Of these, only DINAMO evaluated a fully outpatient approach. No equivalent trial has been conducted in the United States, where antibiotic therapy remains routine for this patient population. Differences in patient demographics, comorbidity burden, healthcare delivery systems, and outpatient follow-up infrastructure may influence the generalizability of prior findings to U.S. populations, sustaining clinical equipoise.

HYPOTHESIS

In adults presenting to the Emergency Department (ED) with acute uncomplicated diverticulitis (modified Hinchey 0 or 1a) and meeting predefined low-risk criteria, outpatient management without antibiotics is non-inferior to standard outpatient antibiotic therapy with respect to diverticulitis-related hospitalization within 6 months.

STUDY DESIGN OVERVIEW

This is a prospective, single-center, open-label, randomized non-inferiority trial. Randomization will be performed in a 1:1 ratio using the REDCap randomization module with a pre-generated allocation table and concealed block sizes. Allocation will be automatically assigned by REDCap upon eligibility confirmation to ensure allocation concealment and reduce selection bias. Recruitment and follow-up will follow the Consolidated Standards of Reporting Trials (CONSORT) statement, including registration of all screened but non-enrolled patients with documented reasons for non-participation.

SETTING AND RECRUITMENT WORKFLOW

All patients presenting to the Emergency Department with signs and symptoms of acute diverticulitis and a CT scan of the abdomen and pelvis reporting acute diverticulitis will be clinically examined by the surgical residents involved in the study and screened for eligibility. Patients who achieve adequate symptom control during ED observation will be approached for informed consent and, if eligible and consenting, enrolled and randomized. Patients who do not achieve adequate symptom control within a maximum of 24 hours of ED observation will be admitted and will not enter the study.

Penicillin allergy status will be ascertained through electronic medical record review and participant self-report, including type of reaction and prior antibiotic tolerance. The study physician will reconcile available information to determine eligibility for the amoxicillin/clavulanate regimen versus the alternative regimen. No formal allergy testing will be performed.

FOLLOW-UP SCHEDULE

• In-person colorectal surgery clinic visit at 1-2 weeks post-enrollment
• Telephone follow-up at 4 weeks, 3 months, and 6 months

A standardized adverse event and symptom questionnaire will be administered at each follow-up timepoint, capturing pain control, gastrointestinal symptoms, fever, medication adherence, treatment- related adverse effects, healthcare utilization, and recurrence. Participants without response after 6 months of attempted contact will be classified as lost to follow-up.

SAMPLE SIZE CALCULATION

Assuming a complication rate of 1% with antibiotic therapy (AVOD) and a maximum acceptable complication rate of 5.8% in the non-antibiotic arm, with one-sided alpha = 0.05 and 80% power, 240 participants per arm are required. Accounting for an anticipated 20% dropout rate, the target enrollment is 278 participants per arm (total N = 556).

STATISTICAL ANALYSIS

Analyses will be performed on both intention-to-treat and per-protocol populations. Categorical variables will be compared using Pearson's chi-square test; continuous variables using independent-samples t-test or non-parametric equivalents as appropriate. Multivariable binary logistic regression will assess the association between baseline covariates and the occurrence of complications. Non-inferiority will be concluded if the upper bound of the one-sided 95% confidence interval for the between-group difference in the primary endpoint lies below the pre-specified non-inferiority margin of 5%. Two-sided alpha = 0.05 will be used for secondary analyses. All analyses will be performed using standard statistical software.

DATA AND SAFETY MONITORING

A formal Data and Safety Monitoring Plan will be implemented, with oversight by the Principal Investigator and an independent faculty monitor not involved in study enrollment or patient management. Monitoring will occur every 2 months and include assessment of recruitment, protocol adherence, data integrity, adverse events, unanticipated problems, complications, treatment failures, and hospitalizations. Interim safety analyses will be conducted periodically. Predefined stopping rules include a clinically or statistically significant excess of adverse outcomes in either arm compared to expected standards of care. Participants will be withdrawn from study interventions in the event of clinical deterioration, progression to complicated diverticulitis, systemic infection, inability to tolerate outpatient management, or at the treating physician's discretion based on safety concerns. Serious adverse events and unanticipated problems will be reported to the IRB and other appropriate institutional entities per institutional policy.

EXPECTED CONTRIBUTION

This study will generate the first prospective U.S.-based randomized evidence on the safety and effectiveness of non-antibiotic outpatient management of acute uncomplicated diverticulitis, informing clinical practice guidelines and antimicrobial stewardship efforts in this population.

• Study Type: Interventional
• Enrollment (Estimated): 556
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yeisson Rivero Moreno, MD; Phone Number: 19178075141; Email: yriveromor@montefiore.org

Study Locations

• United States
  • New York
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
      • Contact: Yeisson Rivero Moreno, MD; Phone Number: 917-807-5141; Email: yriveromor@montefiore.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Left-sided diverticulitis, primary or recurrent
• Signs of diverticulitis on CT-confirmed Hinchey (0 or 1a based on CT final report)
• White Blood Cell (WBC) count <15,000mm^3
• Controlled symptoms in the ED (i.e., Pain score <5 on VAS scale, tolerating PO intake, no fever)

Exclusion Criteria:

• Signs of complicated diverticulitis on CT with abscess, fistula, free air, Micro perforation, or signs of other diagnosis on CT Abdomen and pelvis
• Inflammatory bowel disease
• American Society for Anesthesiologists (ASA) physical status classification of >=3
• Immunocompromised patient; (i.e., haematological malignancies, AIDS patients with low CD4+ counts, transplantation, chemotherapy, splenectomy, long-term corticosteroid use and genetic disorders such as severe combined immunodeficiency
• Pregnancy
• Ongoing antibiotic therapy or in the previous 2 weeks
• High fever, affected general condition, peritonitis or sepsis
• Subjects who do not have the capacity to consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: No-Antibiotic Group; Participants randomized to this arm will be discharged from the Emergency Department with symptomatic treatment only, without antibiotics. The regimen consists of oral ibuprofen 400 mg every 8 hours and/or oral acetaminophen 1 g every 8 hours for symptom control, a liquid diet advancing as tolerated, and standardized return precautions. Participants will receive a patient handout with medication instructions, follow-up schedule, and a dedicated contact number for questions or adverse events.	Drug: Symptomatic treatment (ibuprofen and acetaminophen); Oral ibuprofen 400 mg every 8 hours and/or oral acetaminophen 1 g every 8 hours, taken as needed for pain control for up to 7 days, combined with a liquid diet advancing as tolerated and standardized return precautions. This symptomatic regimen is administered to participants in both study arms.; Other Names: Pain control regimen
Active Comparator: Standard Antibiotic Therapy; Participants randomized to this arm will be discharged from the Emergency Department with standard outpatient antibiotic therapy in addition to symptomatic treatment. The regimen consists of oral amoxicillin/clavulanate 875/125 mg every 12 hours for 7 days, plus oral ibuprofen 400 mg every 8 hours and/or oral acetaminophen 1 g every 8 hours for symptom control, a liquid diet advancing as tolerated, and standardized return precautions. Participants with a documented or self-reported penicillin or beta-lactam allergy will receive oral ciprofloxacin 500 mg every 12 hours plus oral metronidazole 500 mg every 8 hours for 7 days instead of amoxicillin/ clavulanate. Participants will receive a patient handout with medication instructions, follow-up schedule, and a dedicated contact number for questions or adverse events.	Drug: Symptomatic treatment (ibuprofen and acetaminophen); Oral ibuprofen 400 mg every 8 hours and/or oral acetaminophen 1 g every 8 hours, taken as needed for pain control for up to 7 days, combined with a liquid diet advancing as tolerated and standardized return precautions. This symptomatic regimen is administered to participants in both study arms.; Other Names: Pain control regimen; Drug: Amoxicillin-clavulanate; Oral amoxicillin/clavulanate 875/125 mg every 12 hours for 7 days, administered to participants in the antibiotic arm who do not have a documented or self-reported penicillin or beta-lactam allergy. Administered in addition to the symptomatic treatment regimen.; Other Names: Augmentin; Drug: Ciprofloxacin plus metronidazole; Oral ciprofloxacin 500 mg every 12 hours plus oral metronidazole 500 mg every 8 hours for 7 days, administered to participants in the antibiotic arm who have a documented or self-reported penicillin or beta-lactam allergy. Administered in addition to the symptomatic treatment regimen as an alternative to amoxicillin/clavulanate.; Other Names: Cipro plus Flagyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diverticulitis-related hospitalization rate	Diverticulitis-related hospitalization rate will be summarized as a frequency measure. The number/percentage of participants requiring hospital admission for any cause related to acute diverticulitis or its complications, including disease progression, intractable pain, intolerance to oral intake, abscess formation, perforation, or need for surgical intervention will be summarized by study arm. Hospitalizations unrelated to diverticulitis will not be counted.	Up to 6 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Emergency Department revisit rate	Emergency department revisit rate will be summarized as a frequency measure. The number/percentage of participants returning to any Emergency Department for symptoms or complications related to acute diverticulitis after the index ED discharge, regardless of whether the revisit results in hospital admission will be summarized by study arm.	Up to 6 months after enrollment
Progression to complicated diverticulitis	The number/percentage of participants progressing to complicated diverticulitis, defined as modified Hinchey classification stage 1b or higher, documented on repeat CT of the abdomen and pelvis performed during follow-up will be summarized by study arm. The modified Hinchey is a medical staging system that classifies stages of acute diverticulitis as either Stage 0, Stage Ia, Stage Ib, stage II, stage III, or stage IV based on clinical symptoms corroborated by CT imaging, such that higher stages are indicative of increased severity. Findings may include confined pericolic abscess, pelvic or intraabdominal abscess, generalized peritonitis, or fecal peritonitis.	Up to 6 months after enrollment
Need for surgery	The number/percentage of participants requiring surgical intervention related to acute diverticulitis or its complications, including but not limited to drainage of abscess, Hartmann procedure, sigmoid colectomy, or other operative management during the follow-up period, will be summarized by study arm. The number/percentage of participants requiring urgent and emergent surgical intervention will be summarized/reported independently.	Up to 6 months after enrollment
Recurrence of acute diverticulitis	Recurrence of acute diverticulitis will be determined by the number/percentage of participants developing a new episode of acute diverticulitis after complete recovery from the index episode. Recurrence is defined operationally per the American Gastroenterological Association as a new episode of acute diverticulitis occurring after full resolution of a prior incident episode, documented by clinical evaluation and/or imaging.	Up to 6 months after enrollment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain control assessed by Visual Analog Scale	Self-reported pain intensity measured using a 10-point Visual Analog Scale (VAS) where 0 represents no pain and 10 represents the worst imaginable pain, such that higher scores are associated with increased pain intensity. Pain scores will be collected at each follow-up timepoint and summarized by study arm using descriptive statistics.	At 1-2 weeks, 4 weeks, 3 months, and 6 months after enrollment
Treatment-related adverse events	The number/percentage of participants reporting any adverse event related to study treatment, including but not limited to nausea, vomiting, diarrhea, allergic reactions, Clostridioides difficile infection, medication intolerance, or other side effects will be summarized by study arm. Adverse events will be captured at each follow-up timepoint using a standardized questionnaire.	At 1-2 weeks, 4 weeks, 3 months, and 6 months after enrollment
Medication adherence	Medication adherence will be assessed by the number/percentage of participants who self-report completing the prescribed medication regimen as indicated. Adherence will be assessed by participant self-report at the 4-week follow-up, including whether the medication was discontinued before completing the full course. The number/percentage of participants will be summarized by study arm.	At 4 weeks after enrollment

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Investigators: Principal Investigator: James Taylor, MD, Montefiore Medical Center

Publications and helpful links

General Publications

• Stollman N, Smalley W, Hirano I; AGA Institute Clinical Guidelines Committee. American Gastroenterological Association Institute Guideline on the Management of Acute Diverticulitis. Gastroenterology. 2015 Dec;149(7):1944-9. doi: 10.1053/j.gastro.2015.10.003. Epub 2015 Oct 8. No abstract available.
• Hall J, Hardiman K, Lee S, Lightner A, Stocchi L, Paquette IM, Steele SR, Feingold DL; Prepared on behalf of the Clinical Practice Guidelines Committee of the American Society of Colon and Rectal Surgeons. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Treatment of Left-Sided Colonic Diverticulitis. Dis Colon Rectum. 2020 Jun;63(6):728-747. doi: 10.1097/DCR.0000000000001679. No abstract available.
• van Dijk ST, Daniels L, Unlu C, de Korte N, van Dieren S, Stockmann HB, Vrouenraets BC, Consten EC, van der Hoeven JA, Eijsbouts QA, Faneyte IF, Bemelman WA, Dijkgraaf MG, Boermeester MA; Dutch Diverticular Disease (3D) Collaborative Study Group. Long-Term Effects of Omitting Antibiotics in Uncomplicated Acute Diverticulitis. Am J Gastroenterol. 2018 Jul;113(7):1045-1052. doi: 10.1038/s41395-018-0030-y. Epub 2018 May 11.
• Peery AF, Shaukat A, Strate LL. AGA Clinical Practice Update on Medical Management of Colonic Diverticulitis: Expert Review. Gastroenterology. 2021 Feb;160(3):906-911.e1. doi: 10.1053/j.gastro.2020.09.059. Epub 2020 Dec 3.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: May 26, 2026
• First Submitted That Met QC Criteria: May 26, 2026
• First Posted (Actual): June 4, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Outpatients; Anti-Bacterial Agents; Watchful Waiting; Acute Disease; Diverticulitis, Colonic
• Additional Relevant MeSH Terms: Diverticular Diseases; Pathologic Processes; Disease Attributes; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Diverticulosis, Colonic; Pathological Conditions, Signs and Symptoms; Diverticulitis; Acute Disease; Diverticulitis, Colonic; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Azoles; Carboxylic Acids; Imidazoles; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Drug Combinations; Acids, Carbocyclic; Penicillin G; beta-Lactams; Lactams; Clavulanic Acid; Clavulanic Acids; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Nitroimidazoles; Nitro Compounds; Ampicillin; Penicillins; Phenylpropionates; Amoxicillin; Acetaminophen; Metronidazole; Ibuprofen; Amoxicillin-Potassium Clavulanate Combination; Ciprofloxacin
• Other Study ID Numbers: 2025-17516 (Other Identifier: Einstein IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No