ORal Antibiotics In Acute Mesenteric Ischemia

Acute Mesenteric Ischemia Clinical Trial

— ORIAMI  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06387147
• Other study ID #: APHP220818
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: September 1, 2024
• Est. completion date: October 1, 2027

Study information

• Verified date: April 2024
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Alexandre NUZZO, Dr
• Phone: (0)1 40 87 56 57
• Email: alexandre.nuzzo[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 196
• Est. completion date: October 1, 2027
• Est. primary completion date: October 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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 acute intestinal 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 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 (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

Related Conditions & MeSH terms

• Acute Mesenteric Ischemia
• Ischemia
• Mesenteric Ischemia

Intervention

Drug:
• Gentamicin
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
Gentamicin placebo (2ml sodium chloride diluted 1/10 in a syringe of 20mL Metronidazole placebo in tablets
• Metronidazole
Métronidazole 500mg 3 times per day during 14 days oral route or nasogastric tube or jejunostomy tube (in the case of an ostomy)

Locations

Country	Name	City	State
France	Gastroentérologie-Hépatologie Beaujon	Clichy
France	Réanimation - Beaujon	Clichy
France	Chirurgie vasculaire	Paris
France	Réanimation Bichat	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	the rate of intestinal necrosis in the 30 days following the randomisation	occurrence of intestinal necrosis within the 30 days following the randomisation.	30 days after randomisation
Secondary	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	30 days after randomisation
Secondary	the length of intestinal resection at day-30 following the randomisation	total length of intestinal resection at day 30 following the randomisation	30 days after randomisation
Secondary	the occurrence of organ failures within the 30 days following the randomisation	occurrence of organ failure within the 30 days following the randomisation	30 days after randomisation
Secondary	the length of ICU stay	number of days in the intensive care unit	30 days after randomisation
Secondary	the length of hospital stay	number of hospitalization days	30 days after randomisation
Secondary	expected minor side effects during the 14 days of treatment	Occurrence of minor side effects	14 days after randomisation
Secondary	hypersensitivity reactions during the 14 days of treatment	Occurrence of hypersensitivity reaction to antibiotics	14 days after randomisation
Secondary	unexpected or serious adverse event throughout the duration of the study	Occurrence of other adverse events	30 days after randomisation
Secondary	the occurrence of healthcare-associated infection	Occurrence of healthcare-associated infection	30 days after randomisation
Secondary	the gentamicin during the 14 days of treatment	Blood levels of gentamicin at randomisation day , days 7 and 14 after randomisation	14 days after randomisation
Secondary	the metronidazole during the 14 days of treatment	Blood levels of metronidazole at randomisation day, days 7 and 14 after randomisation	14 days after randomisation