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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06387147
Other study ID # APHP220818
Secondary ID
Status Not yet recruiting
Phase Phase 3
First received
Last updated
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
Health authority
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

Study Design


Related Conditions & MeSH terms


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
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