Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
196
Countries
1
Sites
4
Acute mesenteric ischemia
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.
Key facts
- Sponsor
- Assistance Publique Hopitaux De Paris
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Digestive System Diseases [C06]
- Trial duration
- 19 May 2026 → ongoing
- Decision date (initial)
- 2024-07-23
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy
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.
Secondary objectives 3
- To assess the impact of oral antibiotics compare to placebo in AMI patients on: a. the rate of intestinal necrosis in the 30 days following the randomisation b. the all-cause mortality within the 30 days following the randomisation c. the rate of short bowel syndrome (<200cm of remnant small bowel) at day-30 following the randomisation d. the length of intestinal resection at day-30 following the randomisation e. the occurrence of organ failures within the 30 days following the randomisation f. the length of ICU stay g. the length of hospital stay
- To assess the safety of oral antibiotics: a. expected minor side effects during the 14 days of treatment b. hypersensitivity reactions during the 14 days of treatment c. unexpected or serious adverse event throughout the duration of the study d. the emergence of antimicrobial-resistant bacteria during the follow-up (rectal swab) e. the occurrence of healthcare-associated infection
- To evaluate the pharmacokinetics and quantify the blood concentration of: a. the gentamicin during the 14 days of treatment b. the metronidazole during the 14 days of treatment
Conditions and MedDRA coding
Acute mesenteric ischemia
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- 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 16
- 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
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- 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
Secondary endpoints 3
- Oral antibiotics impact assessment endpoints a. occurrence of intestinal necrosis within the 30 days following the randomisation. b. vital status at day-30 after the randomisation c. short bowel syndrome at day-30 after the randomisation d. total length of intestinal resection at day 30 following the randomisation e. occurrence of organ failure within the 30 days following the randomisation f. number of days in the intensive care unit g. number of hospitalization days
- Safety endpoints a. Occurrence of minor side effects b. Occurrence of hypersensitivity reaction to antibiotics c. Occurrence of other adverse events d. Emergence of antimicrobial-resistant microorganisms e. Occurrence of healthcare-associated infection
- Antibiotics’ pharmacokinetic and blood concentration endpoints: a. Blood levels of gentamicin at randomisation day , days 7 and 14 after randomisation b. Blood levels of metronidazole at randomisation day, days 7 and 14 after randomisation
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
GENTAMICINE PANPHARMA 80 mg, solution injectable
PRD648680 · Product
- Active substance
- Gentamicin
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- ORAL, NASOGASTRIC TUBE OR PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE USE
- Max daily dose
- 6 ml millilitre(s)
- Max total dose
- 6 ml millilitre(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01GB03 — GENTAMICIN
- Marketing authorisation
- 34009 351 204 8 9
- MA holder
- PANPHARMA
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
METRONIDAZOLE BIOGARAN 500 mg, comprimé pelliculé
PRD6388005 · Product
- Active substance
- Metronidazole
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL, NASOGASTRIC TUBE OR PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE USE
- Max daily dose
- 1.5 mg milligram(s)
- Max total dose
- 1.5 mg milligram(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- P01AB01, J01XD01 — METRONIDAZOLE, METRONIDAZOLE
- Marketing authorisation
- 3400930147672
- MA holder
- BIOGARAN
- MA country
- France
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 3
Metronidazole Biogaran 500 mg Placebo
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Natriumchlorid-Lösung 0,9 % Deltamedica, Injektionslösung
PRD8768735 · Product
- Active substance
- Sodium Chloride
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- ORAL, NASOGASTRIC TUBE OR PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE USE
- Max daily dose
- 6 ml millilitre(s)
- Max total dose
- 6 ml millilitre(s)
- Max treatment duration
- 14 Day(s)
- Authorisation status
- Authorised
- ATC code
- V07AB — SOLVENTS AND DILUTING AGENTS, INCL. IRRIGATING SOLUTIONS
- Marketing authorisation
- 1299.95.99
- MA holder
- DELTAMEDICA GMBH
- MA country
- Germany
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Assistance Publique Hopitaux De Paris
- Sponsor organisation
- Assistance Publique Hopitaux De Paris
- Address
- Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux
- City
- Paris Cedex 10
- Postcode
- 75475
- Country
- France
Scientific contact point
- Organisation
- Assistance Publique Hopitaux De Paris
- Contact name
- Alexandre Nuzzo
Public contact point
- Organisation
- Assistance Publique Hopitaux De Paris
- Contact name
- Alexandre Nuzzo
Locations
1 EU/EEA country · 4 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| France | Ongoing, recruiting | 196 | 4 |
| Rest of world | — | 0 | — |
Investigational sites
Assistance Publique Hopitaux De Paris
gastroentérologie, 100 Boulevard Du General Leclerc, 92110, Clichy
Assistance Publique Hopitaux De Paris
réanimation, 46 Rue Henri Huchard, 75877, Paris Cedex 18
Assistance Publique Hopitaux De Paris
reanimation, 100 Boulevard Du General Leclerc, 92110, Clichy
Assistance Publique Hopitaux De Paris
chirurgie vasculaire, 46 Rue Henri Huchard, 75877, Paris Cedex 18
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| France | 2025-01-31 | 2025-01-31 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-118715
- Halt date
- 2026-02-09
- Member states concerned
- France
- Publication date
- 2026-02-10
- Reason
- Sponsor decision
- Explanation
- Aucun autre lot disponible
- Follow-up measures
- Monitoring à programmer
Mise en quarantaine des traitements
Suspension des inclusions
Arrêt du traitement du patient en cours - Benefit-risk balance changed
- Yes
- Treatment stopped
- Yes
Urgent safety measures 1 · Art. 54 CTR
Urgent safety measure US-119147
- Event date
- 2026-02-09
- Submission date
- 2026-02-12
- In response to
- OTHER
- Member states affected
- France
- Event description
- On February 9, 2026, the AP-HP (Paris Public Hospitals) received an alert from the PANPHARMA laboratory requesting the recall of batches 40306 and 40306A of PANPHARMA Gentamicin 80 mg injectable solution. This recall follows the detection of possible particulate contamination of some ampoules.
- Measures taken
- The temporary suspension of the research, leading to a new urgent safety measure notification, results both from the lack of an available Treatment Unit to continue the ORIAMI research and from the fact that gentamicin, when administered orally, can exceptionally undergo systemic absorption. Although the risk appears unlikely, the sponsor cannot completely rule out a risk to participants.
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 14 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocole_2023-508249-42-00 fp | 1.2 |
| Protocol (for publication) | D1_Protocole_2023-508249-42-00_v1_1_20240621_clean_fp | 1 |
| Protocol (for publication) | D4_patient facing documents_2023-508249-42-00 | 1 |
| Protocol (for publication) | Summary of clinical and pre-clinical data_2023-508249-42-00 | 1 |
| Protocol (for publication) | Summary of clinical and pre-clinical data_v1_1_2023-508249-42-00_clean | 1 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements_ORIAMI | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangement_v1_2_20240722_ORIAMI clean | 1_2 |
| Recruitment arrangements (for publication) | Liste-investigateurs_v1-0_20240620_ORIAMI | 1 |
| Subject information and informed consent form (for publication) | L1_SIS-ICF adult | 1_3 |
| Subject information and informed consent form (for publication) | L1_SIS-ICF_v1_1_20240620_ORIAMI clean | 1_1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_GENTAMICINE | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC_METRONIDAZOLE BIOGARAN | 1 |
| Synopsis of the protocol (for publication) | D1_Resume-francais_v1_1_20240621_ORIAMI_clean | 1 |
| Synopsis of the protocol (for publication) | D1_Resume-francais_v1_20240412_ORIAMI | 1.2 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-04-15 | France | Acceptable 2024-07-22
|
2024-07-23 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2026-03-27 | France | Acceptable 2026-05-11
|
2026-05-18 |