Per Oral Versus Intravenous Postoperative Antibiotics After Surgery for Complicated Appendicitis.

Study Overview
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Brief Summary
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The PIPA trial is a prospective, multicentre, cluster randomized cluster crossover non-inferiority study. We aim to test whether a three-day postoperative course of per oral antibiotics is non-inferior to a three-day postoperative course of intravenous antibiotics as standard care after laparoscopic surgery for complicated appendicitis in regards to the risk of postoperative intraabdominal abscess formation within 30-days

Detailed Description
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Complicated appendicitis increases the risk of postoperative intra-abdominal abscess. Treatment of complicated appendicitis are usually with a postoperative course of intravenous antibiotics. There is need for a study confirming the results of retrospective studies showing that a postoperative course of oral antibiotics is not inferior to intravenous antibiotics after laparoscopic surgery for complicated appendicitis. The PIPA trial will be a prospective, multicenter, cluster randomized cluster crossover non-inferiority study designed to test whether a three-day postoperative course of per oral antibiotics is non-inferior to a three-day postoperative course of intravenous antibiotics as standard care after laparoscopic surgery for complicated appendicitis in regards to the risk of postoperative intraabdominal abscess formation within 30-days. Participating hospitals will be randomized to either a 6-month period with a per oral antibiotic regime followed by a 6-month period with an intravenous antibiotic regime, or 6-month period with an intravenous antibiotic regime followed by a 6-month period with a per oral antibiotic regime for the postoperative treatment after laparoscopic surgery for complicated appendicitis. Primary outcome will be the incidence of intra-abdominal abscess by the postoperative day 30.

Official Title
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Per Oral Versus Intravenous Postoperative Antibiotics After Surgery for Complicated Appendicitis: A Cluster Randomized Cluster Crossover Non-Inferiority Study.

Conditions
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Complicated Appendicitis

Intervention / Treatment
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* Drug: Antibiotic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: On cluster level, hospitals with emergency surgical admissions performing laparoscopic appendectomies are eligible for inclusion. On an individual level, participants are eligible for inclusion if they undergo a laparoscopic appendectomy for appendicitis (both uncomplicated and complicated), are ≥ 18 years of age, and provide a signed written consent form. Exclusion Criteria: Exclusion criteria are specifically related to the therapy and individual participants will be excluded if they undergo any other procedures than laparoscopic appendectomy during index surgery.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1- Postoperative Course<br>Pre-or intraoperative antibiotics (both uncomplicated and complicated) appendicits: Single-dose inj. Metronidazole and Pipperacillin/Tazobactam. In case of allergy to penicillin: Single-dose inj. Metronidazole and intravenous inj. Cefuroxim. First 6 month: Tablet Amoxicillin/Clavulanic Acid and Tablet Metronidazole.In case of allergy to Penicillin: Tablet Metronidazole and Tablet Ciprofloxacillin. Last 6 month: Intravenous Metronidazole and Intravenous Pipperacillin / Tazobactam. In case of allergy to penicillin: Intravenous Metronidazole and Intravenous Cefuroxim. | Drug: Antibiotic<br>* The study aims to test whether oral antibiotics is non-inferior compared to intravenous antibiotics.<br>* Other names: Amoxicillin / Clavulanic acid;|
| Active Comparator: Arm 2 - Postoperative Course<br>Pre-or intraoperative antibiotics (both uncomplicated and complicated) appendicits: Single-dose inj. Metronidazole and Pipperacillin/Tazobactam. In case of allergy to penicillin: Single-dose inj. Metronidazole and intravenous inj. Cefuroxim. First 6 month: Intravenous Metronidazole and Intravenous Pipperacillin / Tazobactam. In case of allergy to penicillin: Intravenous Metronidazole and Intravenous Cefuroxim. Last 6 month: Tablet Amoxicillin/Clavulanic Acid and Tablet Metronidazole.In case of allergy to Penicillin: Tablet Metronidazole and Tablet Ciprofloxacillin. | Drug: Antibiotic<br>* The study aims to test whether oral antibiotics is non-inferior compared to intravenous antibiotics.<br>* Other names: Amoxicillin / Clavulanic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra-abdominal abscess | Primary outcome is defined as an imaging verified intraabdominal mass treated with drainage or antibiotics, or a surgically verified intra-abdominal abscess | Assessed at postoperative day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| postoperative stay | postoperative length of stay measured in hours | The event is assessed at postoperative day 30. The event is determnied beginning from the time the surgery ends till the time the patient is discharged from the hospital. | 
| Complications according to Clavien-Dindo Classifcation | complications according to the Clavien-Dindo classification at postoperative day 30, that require in- or outpatient treatment, complications grade ≥3a according to Clavien-Dindo Classification at postoperative day 30 | Assessed at postoperative day 30 | 
| Costs | In- and outpatient costs and overall costs of both in-and- outpatient | Assessed at postoperative day 30. Data for both in- and outpatient costs will be extracted from the Danish Health Authority | 
| Wound infection | Postoperative wound infection that require in-and - outpatient treatment. A wound infection is defined as a clinically suspected wound infection which has been treated with an opening of the wound or where antibiotics has been administered for this indication | Assessed postoperative day 30 |