ORal Antibiotics in Acute Mesenteric Ischemia

Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-90
SponsorAssistance Publique - Hôpitaux de Paris

About this trial

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

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Gentamicin

    Drug

    Gentamicin 80 mg 3 times per day during 14 days oral route or nasogastric tube or jejunostomy tube (in the case of an ostomy)

  • Placebo

    Drug

    Gentamicin placebo (2ml sodium chloride diluted 1/10 in a syringe of 20mL Metronidazole placebo in tablets

  • Metronidazole

    Drug

    Métronidazole 500mg 3 times per day during 14 days oral route or nasogastric tube or jejunostomy tube (in the case of an ostomy)

Treatment groups

196 Participants
are divided into 2 treatment groups
Group A: Gentamicin + MetronidazoleExperimental treatment 2 interventions
Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

The primary objective is to assess the efficacy of oral antibiotics compared to placebo on reducing the rate of intestinal necrosis or death (composite primary outcome) in AMI patients within 30 days following the randomisation.

Occurrence of intestinal necrosis or death within 30 days following randomisation defined by the following criteria histology assessment OR all-cause mortality within 30 days following randomisation

Time frame
30 days after randomisation

Secondary outcomes

1

the rate of intestinal necrosis in the 30 days following the randomisation

occurrence of intestinal necrosis within the 30 days following the randomisation.

Time frame
30 days after randomisation
2

the rate of short bowel syndrome (<200cm of remnant small bowel) at day-30 following the randomisation

short bowel syndrome at day-30 after the randomisation

Time frame
30 days after randomisation
3

the length of intestinal resection at day-30 following the randomisation

total length of intestinal resection at day 30 following the randomisation

Time frame
30 days after randomisation
4

the occurrence of organ failures within the 30 days following the randomisation

occurrence of organ failure within the 30 days following the randomisation

Time frame
30 days after randomisation

Other outcomes

Sponsors and contacts

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