RecruitingPhase 3NCT06387147

ORal Antibiotics in Acute Mesenteric Ischemia

ORal Antibiotics in Acute Mesenteric Ischemia: a Multicenter Randomized Controlled Trial

Sponsor

Assistance Publique - Hôpitaux de Paris

Enrollment

196 participants

Start Date

Jan 31, 2025

Study Type

INTERVENTIONAL

Conditions

Acute Mesenteric Ischemia

Summary

Acute mesenteric ischemia (AMI) is a life-threatening condition with an increasing incidence (7-13/100000 PY). The mortality of AMI is associated with the development and extent of transmural intestinal necrosis (IN), ranging from 25% without IN to 75% with IN. Given its potential reversibility, preventing the progression of AMI towards IN is now considered a primary therapeutic goal. Early management of AMI can thus avoid fatal outcomes and prevent lifelong complications such as short bowel syndrome. Following the results of a pilot study showing an improvement in survival and lower resection rates, our team created a first-of-its-kind intestinal stroke center (SURVI unit, Beaujon Hospital, Clichy, France) that provides 24/7 standardized multimodal and multidisciplinary care to AMI patients referred from all hospitals in the Paris region. As no randomized clinical trial has ever been conducted, the treatment offered by SURVI is based on pathophysiological knowledge and observational clinical data. AMI naturally progresses to sepsis, surgical complications, and multi-organ failure, direct consequences of IN. Features of sepsis are reported in up to 90% of AMI patients compared with 3-22% of patients with brain or myocardial ischemia, supporting a specific septic component in AMI. Experimental studies demonstrated reduced translocation and mortality in germ-free animals or after administration of oral antibiotics targeting Gram-negative and anaerobic early bacterial overgrowth and translocation. In a prospective observational study, the investigators recently suggested a protective effect of systematic oral antibiotics in terms of intestinal preservation, yielding a reduced occurrence of IN (HR: 0.16, 95% confidence interval 0.03-0.62). However, the systematic use of oral antibiotics in AMI remains controversial due to the individual and collective risk of increasing the carriage of multi-drug resistant bacterias.

Eligibility

Min Age: 18 YearsMax Age: 90 Years

Inclusion Criteria6

Adult patient aged 18 and less 90
AMI of arterial occlusive origin, defined by the combination of
Onset \< 7 days of clinical, biological and/or radiological signs of acute intestinal injury in the territory of at least superior mesenteric ischemia, including right-side colitis,
significant vascular obstruction \> 75% of the superior mesenteric artery, and
no alternative diagnosis
Admitted to the SURVI care network (Beaujon Hospital intensive care unit or SURVI, Bichat intensive care unit or vascular surgery department)

Exclusion Criteria16

Other forms of mesenteric ischemia (chronic without acute manifestations, venous, non-occlusive, strangulation, aortic dissection)
Isolated left-side ischemic colitis
Mesenteric vascular lesion without small bowel injury or right colon
Not eligible for vascular or digestive surgery or intensive care (palliative context)
Indication for an emergency surgical intestinal resection at the admission to the SURVI care network
Indication for urgent systemic antibiotic treatment on admission (evidence of sepsis defined as a SOFA score of 2 or more associated with an infection)
Systemic or oral antibiotic therapy within 7 days before inclusion
Known hypersensitivity to the active substance /excipients
Contraindications to the investigational medicinal products (gentamicin, metronidazole)
Unable to give consent (under guardianship or curatorship)
Subject deprived of freedom, subject under a legal protective measure
Patient refusal to participate
Non-affiliation to a social security regimen or CMU
Patient under State Medical Aid
Pregnant or breastfeeding women
Participation in another clinical study involving investigational medicinal product or patient being in the exclusion period at the end of a previous study