APLAUD試験（抗生物質対プラセボによる急性単純性憩室炎の治療）
急性単純性憩室炎に対するプラセボと抗生物質の比較
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
調査の概要
状態
条件
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究場所
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Tennessee
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Nashville、Tennessee、アメリカ、37235
- 募集
- Vanderbilt University Medical Center Emergency Department
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コンタクト：
- Alexander T Hawkins, MD, MPH
- 電話番号：+1 (615)343-4612
- メール：alex.hawkins@vumc.org
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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アクティブコンパレータ：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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実験的：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 |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Recruitment Rate
時間枠：From enrollment through study completion, an average of 2 years.
|
Patients recruited per week |
From enrollment through study completion, an average of 2 years.
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Adherence
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Barratt Simplified Measure of Social Status (BSMSS)
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
|
協力者と研究者
出版物と役立つリンク
一般刊行物
- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 251398
- 1R01DK141523-01A1 (米国 NIH グラント/契約)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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