Acute Mesenteric IschemiaPhase 3ORIAMINCT06387147
ORal Antibiotics in Acute Mesenteric Ischemia
A Phase 3 study testing Gentamicin and Metronidazole in people with Acute Mesenteric Ischemia, run by Assistance Publique - Hôpitaux de Paris at 4 sites in France.
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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Acute Mesenteric Ischemia
- What is being tested?
- Gentamicin and Metronidazole
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 196 participants
- Where
- 4 sitesFrance
- Study dates
- 31 Jan 2025to 1 Nov 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
Show all 16Show fewer
- 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
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France4 sites, 4 recruiting
- Recruiting
Gastroentérologie-Hépatologie Beaujon
Clichy, France, 92110
Alexandre NUZZO, Dr, (0)1 40 87 56 57, alexandre.nuzzo@aphp.fr
- Recruiting
Réanimation - Beaujon
Clichy, France, 92110
Emmanuel WEISS, Dr, emmanuel.weiss@aphp.fr
- Not yet recruiting
Chirurgie vasculaire
Paris, France, 75018
Yves Hervé CASTIER, yves.castier@aphp.fr
- Not yet recruiting
Réanimation Bichat
Paris, France, 75018
Brice LORTAT JACOB, Dr, brice.lortat-jacob@aphp.fr
About this study
Official title: ORal Antibiotics in Acute Mesenteric Ischemia: a Multicenter Randomized Controlled 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.
Read the detailed 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.
- Conditions
- Acute Mesenteric Ischemia
- Being tested
- Gentamicin, Placebo, Metronidazole
- Keywords
- necrosis
- Medical subject headings
- Necrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GentamicinDrug
Gentamicin 80 mg 3 times per day during 14 days oral route or nasogastric tube or jejunostomy tube (in the case of an ostomy)
PlaceboDrug
Gentamicin placebo (2ml sodium chloride diluted 1/10 in a syringe of 20mL Metronidazole placebo in tablets
MetronidazoleDrug
Métronidazole 500mg 3 times per day during 14 days oral route or nasogastric tube or jejunostomy tube (in the case of an ostomy)
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Gentamicin; Drug: Metronidazole |
| Placebo | Placebo comparator | Gentamicin placebo (2ml sodium chloride diluted 1/10 in a syringe of 20mL Metronidazole placebo in tablets Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 30 days after randomisation
Secondary outcomes (12)
the rate of intestinal necrosis in the 30 days following the randomisation
occurrence of intestinal necrosis within the 30 days following the randomisation.
Measured: 30 days after randomisation
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
Measured: 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
Measured: 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
Measured: 30 days after randomisation
the length of ICU stay
number of days in the intensive care unit
Measured: 30 days after randomisation
the length of hospital stay
number of hospitalization days
Measured: 30 days after randomisation
expected minor side effects during the 14 days of treatment
Occurrence of minor side effects
Measured: 14 days after randomisation
hypersensitivity reactions during the 14 days of treatment
Occurrence of hypersensitivity reaction to antibiotics
Measured: 14 days after randomisation
unexpected or serious adverse event throughout the duration of the study
Occurrence of other adverse events
Measured: 30 days after randomisation
the occurrence of healthcare-associated infection
Occurrence of healthcare-associated infection
Measured: 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
Measured: 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
Measured: 14 days after randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2024
- Study start31 Jan 2025
- Primary completion1 Nov 2027 (estimated)
- Study completion1 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Mesenteric IschemiaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double-blind Gentamicin + Metronidazole versus placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 196 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Annabelle METOIS, Mrs, Study chair, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06387147
- Sponsor's protocol ID
- APHP220818
- Acronym
- ORIAMI
- Status last verified
- Feb 2025
- First submitted
- 17 Apr 2024
- Last updated
- 19 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ORal Antibiotics in Acute Mesenteric Ischemia: a Multicenter Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06387147
- Acronym / sponsor ID
- ORIAMI / APHP220818
- Conditions
- Acute Mesenteric Ischemia
- Keywords
- necrosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 196 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 31 Jan 2025 (actual)
- Primary completion
- 1 Nov 2027 (estimated)
- Study completion
- 1 Nov 2027 (estimated)
- First posted
- 26 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- double-blind Gentamicin + Metronidazole versus placebo
| Arm | Type | Receives |
|---|---|---|
| Gentamicin + Metronidazole | Experimental | Drug: Gentamicin, Drug: MetronidazoleGentamicin 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 | Drug: PlaceboGentamicin placebo (2ml sodium chloride diluted 1/10 in a syringe of 20mL Metronidazole placebo in tablets |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GentamicinGentamicin 80 mg 3 times per day during 14 days oral route or nasogastric tube or jejunostomy tube (in the case of an ostomy) | Drug | Gentamicin + Metronidazole |
| PlaceboGentamicin placebo (2ml sodium chloride diluted 1/10 in a syringe of 20mL Metronidazole placebo in tablets | Drug | Placebo |
| MetronidazoleMétronidazole 500mg 3 times per day during 14 days oral route or nasogastric tube or jejunostomy tube (in the case of an ostomy) | Drug | Gentamicin + Metronidazole |
Primary outcome
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.
Time frame: 30 days after 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
12 secondary outcomes
the rate of intestinal necrosis in the 30 days following the randomisation
Time frame: 30 days after randomisation
the rate of short bowel syndrome (<200cm of remnant small bowel) at day-30 following the randomisation
Time frame: 30 days after randomisation
the length of intestinal resection at day-30 following the randomisation
Time frame: 30 days after randomisation
the occurrence of organ failures within the 30 days following the randomisation
Time frame: 30 days after randomisation
the length of ICU stay
Time frame: 30 days after randomisation
the length of hospital stay
Time frame: 30 days after randomisation
expected minor side effects during the 14 days of treatment
Time frame: 14 days after randomisation
hypersensitivity reactions during the 14 days of treatment
Time frame: 14 days after randomisation
unexpected or serious adverse event throughout the duration of the study
Time frame: 30 days after randomisation
the occurrence of healthcare-associated infection
Time frame: 30 days after randomisation
the gentamicin during the 14 days of treatment
Time frame: 14 days after randomisation
the metronidazole during the 14 days of treatment
Time frame: 14 days after randomisation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Annabelle METOIS, Mrs study chair
APHP
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Gentamicin and Metronidazole in people with Acute Mesenteric Ischemia, run by Assistance Publique - Hôpitaux de Paris at 4 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 19 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alexandre NUZZO, Dr ((0)1 40 87 56 57, alexandre.nuzzo@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 30 days after randomisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2025.