ORal Antibiotics in Acute Mesenteric Ischemia

NCT06387147 | Recruiting Phase 3 DMC

• 1 other identifier: APHP220818
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Acute Mesenteric Ischemia

Keywords

necrosis

Outcome Measures

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

  30 days after randomisation

Secondary Outcomes (12)

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

  30 days after randomisation

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

  30 days after randomisation

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

  30 days after randomisation

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

  30 days after randomisation

• the length of ICU stay

  30 days after randomisation

Study Arms (2)

Gentamicin + Metronidazole

EXPERIMENTAL

Gentamicin 80 mg Metronidazole 500mg 3 times per day during 14 days oral route or nasogastric tube or jejunostomy tube (in the case of an ostomy)

Drug: Gentamicin; Drug: Metronidazole

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

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)

Gentamicin + Metronidazole

Placebo DRUG

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

Placebo

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)

Gentamicin + Metronidazole

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (4)

Gastroentérologie-Hépatologie Beaujon

Clichy, France, 92110, France

RECRUITING

Réanimation - Beaujon

Clichy, France, 92110, France

RECRUITING

Chirurgie vasculaire

Paris, France, 75018, France

NOT YET RECRUITING

Réanimation Bichat

Paris, France, 75018, France

NOT YET RECRUITING

MeSH Terms

Conditions

Necrosis

Interventions

Gentamicins; Metronidazole

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminoglycosides; Glycosides; Carbohydrates; Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Annabelle METOIS, Mrs

  APHP

  STUDY CHAIR

Central Study Contacts

Alexandre NUZZO, Dr

CONTACT

(0)1 40 87 56 57; alexandre.nuzzo@aphp.fr

Olivier CORCOS, Pr

CONTACT

(0)1 40 87 56 95; olivier.corcos@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: double-blind Gentamicin + Metronidazole versus placebo

Study Record Dates

• First Submitted: April 17, 2024
• First Posted: April 26, 2024
• Study Start: January 31, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: February 19, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4)