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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
|
| Placebo | Placebo Comparator | Gentamicin placebo (2ml sodium chloride diluted 1/10 in a syringe of 20mL Metronidazole placebo in tablets |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| the rate of short bowel syndrome (<200cm of remnant small bowel) at day-30 following the randomisation |
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Inclusion Criteria:
Adult patient aged 18 and less 90
AMI of arterial occlusive origin, defined by the combination of
Admitted to the SURVI care network (Beaujon Hospital intensive care unit or SURVI, Bichat intensive care unit or vascular surgery department)
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| 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 |
| Name | Affiliation | Role |
|---|---|---|
| Annabelle METOIS, Mrs | APHP | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Gastroentérologie-Hépatologie Beaujon | Recruiting | Clichy | France | 92110 | France |
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| ID | Term |
|---|---|
| D009336 | Necrosis |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D005839 | Gentamicins |
| D008795 | Metronidazole |
| ID | Term |
|---|---|
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D009593 | Nitroimidazoles |
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double-blind Gentamicin + Metronidazole versus placebo
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| 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) |
|
short bowel syndrome at day-30 after the randomisation |
| 30 days after randomisation |
| 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 |
| 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 |
| the length of ICU stay | number of days in the intensive care unit | 30 days after randomisation |
| the length of hospital stay | number of hospitalization days | 30 days after randomisation |
| expected minor side effects during the 14 days of treatment | Occurrence of minor side effects | 14 days after randomisation |
| hypersensitivity reactions during the 14 days of treatment | Occurrence of hypersensitivity reaction to antibiotics | 14 days after randomisation |
| unexpected or serious adverse event throughout the duration of the study | Occurrence of other adverse events | 30 days after randomisation |
| the occurrence of healthcare-associated infection | Occurrence of healthcare-associated infection | 30 days after randomisation |
| 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 |
| 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 |
| Réanimation - Beaujon | Recruiting | Clichy | France | 92110 | France |
|
| Chirurgie vasculaire | Not yet recruiting | Paris | France | 75018 | France |
|
| Réanimation Bichat | Not yet recruiting | Paris | France | 75018 | France |
|
| D009574 |
| Nitro Compounds |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |