Antibiotic Therapy vs. Placebo in the Treatment of Acute Uncomplicated Appendicitis: a Randomized Double-blinded Placebo-controlled Trial - APPAC III Study
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 147
- 试验地点
- 1
- 主要终点
- Success of the randomized treatment
研究概览
简要总结
Appendicectomy has been the treatment of acute appendicitis for over a hundred years. Appendicectomy, however, includes operative and postoperative risks despite being a "routine" operation. At the same time other similar intra-abdominal infections, such as diverticulitis, are treated with antibiotics. Several studies have proved promising results of the safety and efficiency of antibiotics in the treatment of acute uncomplicated appendicitis. Our previous APPAC study, published in 2015 in the Journal of American Medical Association, also proved promising results with 73% of patients with CT-diagnosed uncomplicated appendicitis treated successfully with antibiotics within one-year follow-up. None of the patients initially treated with antibiotics that later had appendectomy had major complications. The results of the APPAC trial suggest that CT proven uncomplicated acute appendicitis is not a surgical emergency and antibiotic therapy is a safe first-line treatment option. Reducing unnecessary appendectomies has also been shown to lead to significant economic savings.
Already in 1886 Fitz noted that 1/3 of patients in a large series of autopsies from the pre-appendicectomy era had evidence of prior appendices inflammation suggesting spontaneous resolution of acute appendicitis. Acute appendicitis is thought to be similar to acute diverticulitis ("left-sided appendicitis") and this similarity has been shown in epidemiological studies. Recent studies have shown no benefit of antibiotic treatment in the treatment of uncomplicated diverticulitis with outpatient management without antibiotics proving safe and well-functioning.
The aim of this randomised double-blinded study is to compare antibiotic therapy with placebo to evaluate the role of antibiotic therapy in the resolution of CT-diagnosed uncomplicated acute appendicitis.
The hypothesis is that antibiotic therapy is necessary in the treatment of acute uncomplicated appendicitis and that antibiotic therapy is superior to spontaneous resolution (placebo) with the primary endpoint evaluated at ten days after the intervention.
详细描述
Acute appendicitis is the most common cause of abdominal pain in emergency departments and appendectomy is the most common emergency abdominal surgery. The lifetime risk of acute appendicitis in males is 8.6% and 6.7% in females.In Finland according to Stakes data there were 6 377 appendectomies (3242 in males, 3135 in females, median age 35 years) performed in 2010 with a total number of days in hospital care was 16 111 days and the mean length of hospital stay was three days.
Although acute appendicitis is the most common reason for surgical emergency department visit, its diagnosis still remains challenging. The clinical diagnosis has previously been based on patient history, physical examination and laboratory findings as well as the clinical surgical diagnosis. Several scoring systems have been created to aid in the diagnosis of acute appendicitis18-20, but the accuracy of clinical diagnosis without preoperative imaging is about 76 - 80 % for combined patient groups of males and females.
As acute appendicitis has historically been thought to always progress to perforation requiring emergency appendectomy, high negative appendectomy rates even up to 40 % in some patient populations have been previously accepted as good surgical practice. For the last two decades, the use of dedicated imaging in acute abdomen in general and also in acute appendicitis has led to improved diagnostic accuracy.
Based on large epidemiological studies, it is now known that complicated (perforated) and uncomplicated (non-perforated) appendicitis have followed different epidemiological trends. These unassociated epidemiologic trends suggest different pathophysiology for the two form of appendicitis. The differential diagnosis is essential as patients with an uncomplicated acute appendicitis may not require surgical intervention and might experience even spontaneous resolution without perforation. The majority (approximately 80 %) of acute appendicitis cases are of uncomplicated nature.
Complicated acute appendicitis defined as a finding of a perforation, appendicolith, abscess or a suspicion of a tumor, requires emergency appendectomy with the exception of cases with abscess as they are often managed conservatively.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double-blinded RCT, no care providers, patients or researchers are aware of the randomised treatment. Separate safety monitoring committee and preplanned interim analysis.
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18-60 years
- •CT confirmed uncomplicated acute appendicitis
- •Ability to give informed consent
排除标准
- •Age under 18 or over 60 years
- •Pregnancy or lactation
- •Allergy to contrast media or iodine
- •Allergy or contraindication to antibiotic therapy
- •Metformin medication
- •Renal insufficiency
- •Severe systemic illness (for example malignancy, medical condition requiring immunosuppressant medication)
- •Complicated acute appendicitis confirmed by CT scan
- •Inability to cooperate or give informed consent
研究组 & 干预措施
Antibiotic treatment
Ertapenem 1 g x 1 intravenously for 3 days, followed by per oral levofloxacin 500 mg x 1 and metronidazole 500 mg x 3 for 4 days, duration of treatment 7 days.
干预措施: Ertapenem (Drug)
Placebo
Intravenous placebo once a day for 3 days, followed by per oral placebo for 4 days with similar p.o. tablets as in the antibiotic group.
干预措施: Placebo (Other)
结局指标
主要结局
Success of the randomized treatment
时间窗: 10 days after treatment initiation
Resolution of acute appendicitis with study group treatment resulting in discharge from the hospital without the need for surgical intervention and treatment efficacy evaluated at ten days after initiation of the randomized treatment.
次要结局
- Hospital stay(1 month)
- VAS score (visual analogue score)(10 years)
- Late recurrence of appendicitis(10 years)
- Post-intervention complications(10 years)
- Sick leave(1 month)
- Treatment costs(10 years)
研究者
Paulina Salminen
Primary investigator
Turku University Hospital