2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial

E. M.L.(Elisabeth) de Wijkerslooth, Evert Jan G. Boerma, APPIC Study Group, C. C.(Charles) van Rossem, J. (Joost) van Rosmalen, Coen I.M. Baeten, F. H.(Frederique) Beverdam, Johanna W.A.M. Bosmans, E. C.J.(Esther) Consten, J. W.T.(Jan Willem) Dekker, Marloes Emous, Anna A.W. van Geloven, Anton F. Gijsen, Luc A. Heijnen, An P. Jairam, Damian C. Melles, Augustinus P.T. van der Ploeg, P. (Pascal) Steenvoorde, B. R.(Boudewijn) Toorenvliet, Maarten VermaasBas Wiering, B. P.L.(Bas) Wijnhoven*, A. L.(Anne Loes) van den Boom*, C. I.M.(Coen) Baeten, F. H.(Frederique) Beverdam, E. G.(Evert Jan) Boerma, J. W.A.M.(Anne Claire) Bosmans, T. A.(Thijs) Burghgraef, E. C.J.(Esther) Consten, J. W.T.(Jan Willem) Dekker, M. (Marloes) Emous, A. A.W.(Nanette) van Geloven, A. F.(Anton) Gijsen, S. A.(Sander) Huisman, An P. Jairam, P. T.J.H.M.(Paul) Janssen, S. (Sanne) Klaphake, L. F.(Leonard) Kroese, H. R.(Hester) Langeveld, Damian C. Melles, B. J.(Bo) Noordman, J. (Joost) van Rosmalen, Maarten Vermaas, J. (Joël) Shapiro, J. (Joost) Verhelst, H. P.(Hendt) Versteegh, J. L.A.(Jeroen) van Vugt, B. J.(Bart) van Wijk, B. P.L.(Bas) Wijnhoven

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Scopus)

Abstract

Background: The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. Methods: In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. Findings: Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI −1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. Interpretation: 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. Funding: The Netherlands Organization for Health Research and Development.

Original languageEnglish
Pages (from-to)366-376
Number of pages11
JournalThe Lancet
Volume401
Issue number10374
DOIs
Publication statusPublished - 4 Feb 2023

Bibliographical note

Funding:
The Netherlands Organization for Health Research and Development.



Funding Information:
This trial was supported by The Netherlands Organization for Health Research and Development, grant number 848015008. We thank the patients for their participation in this study and local surgical residents for their contribution to patient recruitment. We thank D Rizopoulos, W A Bemelman, L P S Stassen, and A Muller for participation in the data safety and monitoring board.

Publisher Copyright:
© 2023 Elsevier Ltd

Fingerprint

Dive into the research topics of '2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial'. Together they form a unique fingerprint.

Cite this