Peritonitis Diverticular: ¿Qué Nos Enseñó Ladies Trial? Análisis Metodológico de su Diseño, Aplicación y Resultados

Abstract

Background: LADIES TRIAL is considered one of the most important trials related to diverticular peritonitis. Its protocol and results were published in 2010, 2015, 2017, and 2019. Despite this one and other published trials, the proper procedures for each diverticular peritonitis scenario are still being debated, a thorough review of the methodology used in this trial is necessary to validate or reject their conclusions.
Aim: To analyze the methodology used in the design, application, analysis of results, and conclusions of all LADIES TRIAL publications. Secondly, to collaborate in the improvement of the research about diverticular peritonitis and to facilitate its analysis by the readers.
Methods: The central parts of a research trial were analyzed, from the research question, hypothesis development, operationalization of variables and trial design, statistical analysis of results, to conclusions. Errors, biases and weaknesses were searched for to try and challenge the trial's findings.
Results: LADIES was a randomized, open-label, superiority trial analyzed according to intention to treat modified in cases of non-compliance with the inclusion-exclusion criteria. Its design was generally correct, although errors, weaknesses, and biases were detected in its application. Regarding results, LOLA showed that, in Hinchey 3, laparoscopic lavage has a higher rate in early morbidity and mortality than sigmoidectomy, but with a shorter operative time. For its part, DIVA showed that, in Hinchey 3 and 4, the primary anastomosis has higher ostomy-free survival with less morbidity, combining the initial surgery and ostomy closure, compared to the Hartmann procedure.
Conclusions: Not having reached the sample size calculated in its design implies that only large effect differences achieved statistical significance. The low frequencies of adverse events accentuated this methodological problem. The specialization of the intervening centers and surgeons, the exclusion of hemodynamically unstable patients or patients undergoing steroid therapy, compromised the external validation of their findings.