ORal Antibiotics in Acute Mesenteric Ischemia

Last updated: February 17, 2025
Sponsor: Assistance Publique - Hôpitaux de Paris
Overall Status: Active - Recruiting

Phase

3

Condition

Occlusions

Treatment

Placebo

Metronidazole

Gentamicin

Clinical Study ID

NCT06387147
APHP220818
  • Ages 18-90
  • All Genders

Study 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 Criteria

Inclusion

Inclusion Criteria:

  • Adult patient aged 18 and less 90

  • AMI of arterial occlusive origin, defined by the combination of

  1. Onset < 7 days of clinical, biological and/or radiological signs of acuteintestinal injury in the territory of at least superior mesenteric ischemia,including right-side colitis,

  2. significant vascular obstruction > 75% of the superior mesenteric artery, and

  3. 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

Exclusion Criteria:

  • 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 (palliativecontext)

  • Indication for an emergency surgical intestinal resection at the admission to theSURVI care network

  • Indication for urgent systemic antibiotic treatment on admission (evidence of sepsisdefined 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 productor patient being in the exclusion period at the end of a previous study

Study Design

Total Participants: 196
Treatment Group(s): 3
Primary Treatment: Placebo
Phase: 3
Study Start date:
January 31, 2025
Estimated Completion Date:
November 01, 2027

Study Description

After the screening visit and informed consent collected by the recruiting investigator, all consecutive eligible patients (who will meet all inclusion criteria and none of exclusion criteria) will be included and randomized double-blind to oral antibiotics or double placebo group.

Patients will be evaluated at days 1, 3, 7, 14, 21 and 30 after the randomisation.

Connect with a study center

  • Gastroentérologie-Hépatologie Beaujon

    Clichy, 92110
    France

    Active - Recruiting

  • Réanimation - Beaujon

    Clichy, 92110
    France

    Active - Recruiting

  • Chirurgie vasculaire

    Paris, 75018
    France

    Site Not Available

  • Réanimation Bichat

    Paris, 75018
    France

    Site Not Available

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