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

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

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

Study Overview

• Status: Completed
• Conditions: Complicated Appendicitis
• Intervention / Treatment: Drug: Antibiotic

Detailed Description

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.

The study duration has been extended by three months in both arms, totaling six months, due to insufficient patient recruitment. By addressing this challenge, the research team seeks to achieve a more representative sample size to ensure robust and reliable research outcomes.

• Study Type: Interventional
• Enrollment (Actual): 3193
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Slagelse, Denmark, 4200
    • Slagelse Hospital, Department of Surgery
  • Slagelse, Denmark
    • Department of Surgery, Slagelse Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1- Postoperative Course; 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; The study aims to test whether oral antibiotics is non-inferior compared to intravenous antibiotics.; Other Names: metronidazole intravenous; metronidazole oral; Piperacillin / Tazobactam; Amoxicillin / Clavulanic acid
Active Comparator: Arm 2 - Postoperative Course; 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; The study aims to test whether oral antibiotics is non-inferior compared to intravenous antibiotics.; Other Names: metronidazole intravenous; metronidazole oral; Piperacillin / Tazobactam; Amoxicillin / Clavulanic acid

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zealand University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): May 31, 2024
• Study Completion (Actual): June 30, 2024

Study Registration Dates

• First Submitted: February 27, 2021
• First Submitted That Met QC Criteria: March 16, 2021
• First Posted (Actual): March 17, 2021

Study Record Updates

• Last Update Posted (Actual): October 1, 2024
• Last Update Submitted That Met QC Criteria: September 30, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Cecal Diseases; Intraabdominal Infections; Appendicitis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; beta-Lactamase Inhibitors; Metronidazole; Anti-Bacterial Agents; Amoxicillin; Clavulanic Acid; Clavulanic Acids; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination
• Other Study ID Numbers: P-2021-27

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No