APLAUD-studien (Antibiotika vs Placebo for akutt ukomplisert divertikulitt)
Sammenligning av placebo mot antibiotika for akutt ukomplisert divertikulitt
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
Studieoversikt
Status
Forhold
Studietype
Registrering (Antatt)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
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Tennessee
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Nashville, Tennessee, Forente stater, 37235
- Rekruttering
- Vanderbilt University Medical Center Emergency Department
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Ta kontakt med:
- Alexander T Hawkins, MD, MPH
- Telefonnummer: +1 (615)343-4612
- E-post: alex.hawkins@vumc.org
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-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Firemannsrom
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Aktiv komparator: 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. |
amoxicillin-clavulanate:1 tablet [875 mg amoxicillin; 125 mg clavulanic acid] every 8 hours metronidazole: 500 mg every 12 hours cefuroxime: 500 mg every 12 hours |
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Eksperimentell: Placebo
A placebo matching the antibiotic arm's treatment regimen will be administered for 10 days |
A placebo matching the antibiotic arm's treatment regimen will be administered for 10 days |
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Recruitment Rate
Tidsramme: From enrollment through study completion, an average of 2 years.
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Patients recruited per week |
From enrollment through study completion, an average of 2 years.
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Adherence
Tidsramme: From enrollment through study completion, an average of 2 years
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Percent of patients completing the course of antibiotics/placebo |
From enrollment through study completion, an average of 2 years
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Data completeness
Tidsramme: 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
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Retention
Tidsramme: From enrollment through study completion, an average of 2 years
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Percentage of patients completing all study activities |
From enrollment through study completion, an average of 2 years
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Acceptability
Tidsramme: Collected at 14 days and 6 months
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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
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Cross over
Tidsramme: From enrollment through study completion, an average of 2 years
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Defined as the number of placebo subjects that ended up being treated with antibiotics |
From enrollment through study completion, an average of 2 years
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Barratt Simplified Measure of Social Status (BSMSS)
Tidsramme: Collected at the time of enrollment
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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
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Brief Health Literacy Scale (BHLS)
Tidsramme: Collected at enrollment
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3-item questionnaire, scored on a scale of 1-5 with 5 being the highest degree of health literacy |
Collected at enrollment
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Patient-Reported Outcomes Measurement Information System-10 (PROMIS-10)
Tidsramme: Collected at the time of enrollment, 30 days, and 6 months
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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
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Diverticulitis quality of life (DV-QOL) instrument
Tidsramme: Collected at enrollment, then 14 and 30 days into the study.
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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.
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Patient-Reported Outcomes Measurement Information System, Gastrointestinal
Tidsramme: Collected at enrollment and 14 days into study
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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
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Time to normalization of abdominal pain intensity
Tidsramme: Collected at enrollment, daily for 30 days, and at 6 months
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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
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Rate of Progression to Complicated Diverticulitis
Tidsramme: Collected at enrollment, 14 days, 30 days, and 6 months
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Captured via review of the EMR and any follow up CT scans |
Collected at enrollment, 14 days, 30 days, and 6 months
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Rate of persistent diverticulitis at 30 days
Tidsramme: Collected 30 days from enrollment
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DV-QOL scores below the patient acceptable symptom state threshold of 3.2/10 |
Collected 30 days from enrollment
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Rate of diverticulitis-related hospitalization, percutaneous drainage and colectomy
Tidsramme: From enrollment through study completion, an average of 2 years
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Collected from EMR and patient queries |
From enrollment through study completion, an average of 2 years
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Mortality
Tidsramme: From enrollment through study completion, an average of 2 years
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Obtained from Social Security Administration Death Master File |
From enrollment through study completion, an average of 2 years
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Adverse Drug Events
Tidsramme: From enrollment through study completion, an average of 2 years
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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
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Return to normal activity
Tidsramme: 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
|
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Recurrence
Tidsramme: From 8 weeks into the study through study completion, an average of 2 years
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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
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Samarbeidspartnere og etterforskere
Samarbeidspartnere
Publikasjoner og nyttige lenker
Generelle publikasjoner
- Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009 Apr;42(2):377-81. doi: 10.1016/j.jbi.2008.08.010. Epub 2008 Sep 30.
- Weiner BJ, Lewis CC, Stanick C, Powell BJ, Dorsey CN, Clary AS, Boynton MH, Halko H. Psychometric assessment of three newly developed implementation outcome measures. Implement Sci. 2017 Aug 29;12(1):108. doi: 10.1186/s13012-017-0635-3.
- Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics. 1993 Nov;4(5):353-65. doi: 10.2165/00019053-199304050-00006.
- Cella D, Riley W, Stone A, Rothrock N, Reeve B, Yount S, Amtmann D, Bode R, Buysse D, Choi S, Cook K, Devellis R, DeWalt D, Fries JF, Gershon R, Hahn EA, Lai JS, Pilkonis P, Revicki D, Rose M, Weinfurt K, Hays R; PROMIS Cooperative Group. The Patient-Reported Outcomes Measurement Information System (PROMIS) developed and tested its first wave of adult self-reported health outcome item banks: 2005-2008. J Clin Epidemiol. 2010 Nov;63(11):1179-94. doi: 10.1016/j.jclinepi.2010.04.011. Epub 2010 Aug 4.
- Hays RD, Bjorner JB, Revicki DA, Spritzer KL, Cella D. Development of physical and mental health summary scores from the patient-reported outcomes measurement information system (PROMIS) global items. Qual Life Res. 2009 Sep;18(7):873-80. doi: 10.1007/s11136-009-9496-9. Epub 2009 Jun 19.
- Chabok A, Pahlman L, Hjern F, Haapaniemi S, Smedh K; AVOD Study Group. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012 Apr;99(4):532-9. doi: 10.1002/bjs.8688. Epub 2012 Jan 30.
- Biondo S, Golda T, Kreisler E, Espin E, Vallribera F, Oteiza F, Codina-Cazador A, Pujadas M, Flor B. Outpatient versus hospitalization management for uncomplicated diverticulitis: a prospective, multicenter randomized clinical trial (DIVER Trial). Ann Surg. 2014 Jan;259(1):38-44. doi: 10.1097/SLA.0b013e3182965a11.
- Ambrosetti P, Becker C, Terrier F. Colonic diverticulitis: impact of imaging on surgical management -- a prospective study of 542 patients. Eur Radiol. 2002 May;12(5):1145-9. doi: 10.1007/s00330-001-1143-y. Epub 2001 Nov 8.
- Chew LD, Bradley KA, Boyko EJ. Brief questions to identify patients with inadequate health literacy. Fam Med. 2004 Sep;36(8):588-94.
- 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.
- Spiegel BM, Reid MW, Bolus R, Whitman CB, Talley J, Dea S, Shahedi K, Karsan H, Teal C, Melmed GY, Cohen E, Fuller G, Yen L, Hodgkins P, Erder MH. Development and validation of a disease-targeted quality of life instrument for chronic diverticular disease: the DV-QOL. Qual Life Res. 2015 Jan;24(1):163-79. doi: 10.1007/s11136-014-0753-1. Epub 2014 Jul 25.
- W. B. The Barratt Simplified Measure of Social Status (BSMSS) measuring SES. 2006. Accessed 8/11/22, https://www.wbarratt.indstate.edu/socialclass/Barratt Simplifed Measure of Social Status.pdf
- Spiegel BM, Hays RD, Bolus R, Melmed GY, Chang L, Whitman C, Khanna PP, Paz SH, Hays T, Reise S, Khanna D. Development of the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) gastrointestinal symptom scales. Am J Gastroenterol. 2014 Nov;109(11):1804-14. doi: 10.1038/ajg.2014.237. Epub 2014 Sep 9.
- Ribas Y, Bombardo J, Aguilar F, Jovell E, Alcantara-Moral M, Campillo F, Lleonart X, Serra-Aracil X. Prospective randomized clinical trial assessing the efficacy of a short course of intravenously administered amoxicillin plus clavulanic acid followed by oral antibiotic in patients with uncomplicated acute diverticulitis. Int J Colorectal Dis. 2010 Nov;25(11):1363-70. doi: 10.1007/s00384-010-0967-9. Epub 2010 Jun 5.
- Balasubramanian I, Fleming C, Mohan HM, Schmidt K, Haglind E, Winter DC. Out-Patient Management of Mild or Uncomplicated Diverticulitis: A Systematic Review. Dig Surg. 2017;34(2):151-160. doi: 10.1159/000450865. Epub 2016 Oct 5.
- Ridgway PF, Latif A, Shabbir J, Ofriokuma F, Hurley MJ, Evoy D, O'Mahony JB, Mealy K. Randomized controlled trial of oral vs intravenous therapy for the clinically diagnosed acute uncomplicated diverticulitis. Colorectal Dis. 2009 Nov;11(9):941-6. doi: 10.1111/j.1463-1318.2008.01737.x. Epub 2008 Nov 7.
- Qaseem A, Etxeandia-Ikobaltzeta I, Lin JS, Fitterman N, Shamliyan T, Wilt TJ; Clinical Guidelines Committee of the American College of Physicians*; Crandall CJ, Cooney TG, Cross JT Jr, Hicks LA, Maroto M, Mustafa RA, Obley AJ, Owens DK, Tice J, Williams JW Jr; Clinical Guidelines Committee of the American College of Physicians. Diagnosis and Management of Acute Left-Sided Colonic Diverticulitis: A Clinical Guideline From the American College of Physicians. Ann Intern Med. 2022 Mar;175(3):399-415. doi: 10.7326/M21-2710. Epub 2022 Jan 18.
- 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.
- Francis NK, Sylla P, Abou-Khalil M, Arolfo S, Berler D, Curtis NJ, Dolejs SC, Garfinkle R, Gorter-Stam M, Hashimoto DA, Hassinger TE, Molenaar CJL, Pucher PH, Schuermans V, Arezzo A, Agresta F, Antoniou SA, Arulampalam T, Boutros M, Bouvy N, Campbell K, Francone T, Haggerty SP, Hedrick TL, Stefanidis D, Truitt MS, Kelly J, Ket H, Dunkin BJ, Pietrabissa A. EAES and SAGES 2018 consensus conference on acute diverticulitis management: evidence-based recommendations for clinical practice. Surg Endosc. 2019 Sep;33(9):2726-2741. doi: 10.1007/s00464-019-06882-z. Epub 2019 Jun 27.
- Mora-Lopez L, Ruiz-Edo N, Estrada-Ferrer O, Pinana-Campon ML, Labro-Ciurans M, Escuder-Perez J, Sales-Mallafre R, Rebasa-Cladera P, Navarro-Soto S, Serra-Aracil X; DINAMO-study Group. Efficacy and Safety of Nonantibiotic Outpatient Treatment in Mild Acute Diverticulitis (DINAMO-study): A Multicentre, Randomised, Open-label, Noninferiority Trial. Ann Surg. 2021 Nov 1;274(5):e435-e442. doi: 10.1097/SLA.0000000000005031.
- 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. Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis. Br J Surg. 2017 Jan;104(1):52-61. doi: 10.1002/bjs.10309. Epub 2016 Sep 30.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Svovelforbindelser
- Organiske kjemikalier
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Heterocykliske forbindelser, 2-ring
- Heterocykliske forbindelser, smeltet ringen
- Farmasøytiske preparater
- Azoler
- Imidazoles
- Amides
- Medikamentkombinasjoner
- Penicillin g
- Beta-laktams
- Laktams
- Clavulansyre
- Clavulansyrer
- Cephalosporins
- Tiaziner
- Nitroimidazoler
- Nitroforbindelser
- Ampicillin
- Penicillins
- Amoxicillin
- Metronidazol
- Amoksicillin-kaliumklavulanat kombinasjon
- Cefuroksim
Andre studie-ID-numre
- 251398
- 1R01DK141523-01A1 (U.S. NIH-stipend/kontrakt)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Legemiddel- og utstyrsinformasjon, studiedokumenter
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