The goal of this study is to evaluate efficacy and safety of stopping postoperative antibiotic treatment after 48 hours of intravenous therapy versus continuing for three more days (to complete a total of five days which is common practice),…
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome of this study is a composite endpoint of mortality and
infectious complications related to appendectomy including intra-abdominal
abscess and surigical site infection. You will find a more detailed definition
of the primary endpoint in Chapter 8 (Methods) of the studyprotocol, on page
29.
Secondary outcome
Secundary outcomes are amongst others: intra-abdominal abscess, superficial
and/or deep surgical site infections, restart of antibiotics, hospital stay in
hours, readmission rate and cost-effectiveness.
Study variables are: age at time of diagnosis, location of operation, medical
history (including diabetes mellitus, corticosteroid use), ASA score, gender,
BMI, body temperature and laboratory results at time of presentation (CRP, WBC,
eGFR), diagnostic radiological imaging, duration and severity of abdominal pain
(VAS scale), antibiotic use prior to clinical diagnosis of acute appendicitis
(type and dosage), prophylactic antibiotic use (type and dosage), laparoscopic
or open appendectomy, duration of operation (skin-to-skin time), type of
appendicitis (phlegmonous, gangrenous or perforated, with or without abscess),
degree of peritonitis, level of expertise of surgeon, peritoneal irrigation
and/or suction, wound management, use of (endo)loops or (endo)stapler,
intraperitoneal drain placement, cultures of intra-abdominal fluid collections,
histological type of appendicitis, (time to reach) discharge criteria,
postoperative imaging for suspected complications, intra-abdominal abscess
(IAA), deep and/or superficial surgical site infection (SSI), treatment of IAAs
and SSIs, any other postoperative complication including severity, duration and
doses of antibiotics received, restart of antibiotics and type, adverse events
on antibiotics, type and resistance profile of cultured micro-organisms
postoperatively, length of hospital stay, post-operative outpatient visit,
readmission, re-interventions for complications (all within 90 days after
appendectomy).
Background summary
Acute appendicitis is an inflammation of the appendix. In the Netherlands,
approximately 16.000 patients undergo appendectomy annually. After appendectomy
for uncomplicated appendicitis most patients can be discharged within 24-48
hours. However, in 25%-30% of the patients, a complex appendicitis is diagnosed
for which guidelines dictate postoperative intravenous antibiotics to reduce
the rate of infectious complications. There is currently no consensus on the
duration of postoperative antibiotics and randomized clinical studies are
lacking. Cohort studies suggest there is no difference in infectious
complications when comparing three to five days of postoperative antibiotics.
To minimize hospital stay, costs and the risk of bacterial resistance, it is
important to define a safe and effective antibiotic regimen. There is an urgent
need for a high-quality study assessing the appropriate duration of
postoperative antimicrobial therapy for complex appendicitis in both children
and adults.
Study objective
The goal of this study is to evaluate efficacy and safety of stopping
postoperative antibiotic treatment after 48 hours of intravenous therapy versus
continuing for three more days (to complete a total of five days which is
common practice), following appendectomy in patients suffering from complex
appendicitis. The primary endpoint is a composite endpoint of mortality and
infectious complications related to appendectomy, including intra-abdominal
abscess and surgical site infections, within 90 days after appendectomy.
Secondary objectives are cost-effectiveness, intra-abdominal abscess,
superficial and/or deep surgical site infections, mortality, duration of
postoperative antibiotic treatment, re-start of antibiotics, hospital stay in
hours from the operation, time to reach discharge criteria in hours from the
operation, emergency room visits, readmission rate and adverse events on
antibiotics (all within 90 days after appendectomy).
Study design
Non-inferiority, multicentre, randomized clinical trial comparing two
postoperative treatment strategies of antibiotics for complex acute
appendicitis.
Intervention
Patients will be randomized to either A) stopping antbiotic treatment after 48
hours of intravenous antibiotics (intervention group), or B) continuing
antibiotic treatment for three more days (control group). Antibiotics given
intravenously are cefuroxime and metronidazole. Alternatively, the combination
of ceftriaxone and metronidazole is allowed, if preferred due to local
bacterial resistance patterns. In children < 40kg the doses will be adjusted
according to their weight.
Study burden and risks
Treatment of complex acute appendicitis with the proposed antibiotics is common
practice in the Netherlands. These antibiotic regimens have been widely used
for a long time already and toxicity and possible side effects are well
documented. Therefore no extra risks are associated with the medicinal
products. The risk of reducing antibiotic treatment in the intervention group
in terms of a possibly higher rate of infectious complications is considered
low. To closely monitor clinically important adverse events, an independent
safety committee (DSMB) is established. Personal benefit for patients in the
intervention group in terms of patient comfort may be shorter hospital stay. No
extra burden is associated with trial-participation in the context of blood
samples taken, number of site visits and other physical examination or tests.
The only difference compared to standard practice is one extra follow-up by
phone and a productivity cost questionnaire.
s-Gravendijkwal 230
Rotterdam 3015CE
NL
s-Gravendijkwal 230
Rotterdam 3015CE
NL
Listed location countries
Age
Inclusion criteria
- age minimum 8 years old (no upper limit)
- patients with suspected acute appendicitis, awaiting appendectomy
- written informed consent
- intraoperative diagnosis of a complex appendicitis*;*A complex appendicitis includes a gangrenous and/or perforated appendicitis, as well as appendicitis with an abscess. For more information and details regarding severity of appendicitis, see 4.1 Population in the studyprotocol (page 19).
Exclusion criteria
- not able to give informed consent
- appendectomy à froid
- severe sepsis, defined as sepsis-induced tissue hypoperfusion or organ dysfunction
- conservative treatment of acute appendicitis
- ASA score IV or not able to undergo surgery
- known allergy or any other contraindication for the use of the study medication
- immunocompromised patients
- pregnancy
- use of other antibiotics
- intraoperative diagnosis of a simple appendicitis
- intraoperative appendicular infiltration not amendable for appendectomy
- inadequate source control after appendectomy*;*the definition of adequate source control is given in the studyprotocol
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-003428-21-NL |
| CCMO | NL59492.078.16 |
| Other | NTR-6128 |
| OMON | NL-OMON24288 |