Pneumonia, Ventilator-AssociatedPhase 3AMIKINHALNCT03149640
Study Comparing Inhaled Amikacin Versus Placebo to Prevent Ventilator Associated Pneumonia
A Phase 3 study testing Inhaled amikacin in people with Pneumonia, Ventilator-Associated, run by University Hospital, Tours at 18 sites in France.
Trial summary
The objective of the study is to prove that after the third day of invasive mechanical ventilation a three-day course of inhaled amikacin reduces the incidence of subsequent VAP. Parallel two group double blind randomized controlled clinical trial. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pneumonia, Ventilator-Associated
- What is being tested?
- Inhaled amikacin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 850 participants
- Where
- 18 sitesFrance
- Study dates
- 19 Jul 2017to 17 Jun 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years the day of inclusion
- Mechanical ventilation through an endotracheal tube for more than three consecutive days (72h)
- Written informed consent of the patient or a proxy
- Patients covered by or having the rights to French social security
- Negative pregnancy test, at the time of inclusion, in women of childbearing potential
Who cannot join
- Suspicion or confirmed VAP the day of inclusion
- Clinical indication for systemic aminoglycoside therapy the day of inclusion : as deemed necessary by the clinician in charge
- Stage 2 or 3 KDIGO* classification acute kidney injury the day of inclusion excepted in patients undergoing renal replacement therapy
- Chronic kidney failure : baseline glomerular filtration lower than 30 mL/min
- Patient scheduled for extubation within the next 24h
- Patient ventilated through an endotracheal tube for more than four consecutive days before inclusion (96h)
Show all 12Show fewer
- Patient ventilated through a tracheostomy
- Patients allergic to aminoglycosides
- Myasthenia gravis
- Known pregnant women at the time of inclusion and lactating patients
- Known guardianship or trusteeship at the time of inclusion
- Patients previously included in this study
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
France18 sites
Service de Réanimation Chirurgicale
Angers, 49933
Service de Réanimation Médicale - CH d'Angoulême
Angoulême, 16959
Service de Réanimation Polyvalente
Argenteuil
Service de Réanimation Médicale - Hôpital Louis Mourier
Colombes, 92700
Service de Réanimation
Dijon, 21079
Service de Réanimation Médicale - CHD Les Oudairies
La Roche-sur-Yon, 85025
Service de Réanimation
Le Mans, 72037
Service de Réanimation Médicale - Hôpital La Croix-Rousse
Lyon, 69317
Service de Réanimation Médicale
Orléans, 45100
Service de Réanimation Médicale - Hôpital Pitié Salpêtrière
Paris, 75013
Service de Réanimation Médicale - CHU La Milétrie
Poitiers, 86021
Service de Réanimation Médicale
Poitiers, 86021
Service de Réanimation Médicale - CHU Pontchaillou
Rennes, 35033
Service de Réanimation Médicale - CHU Rouen
Rouen, 76031
Service de Réanimation Médicale - Hôpital Charles Nicolle
Rouen, 76031
Service de Réanimation - NHC
Strasbourg, 67091
Service de Réanimation Médicale - Hôpital de Hautepierre
Strasbourg, 67098
Service de Réanimation médicale, Hôpital Trousseau
Tours, 37044
About this study
Official title: Double-blinded Multicenter Randomized Controlled Trial Comparing Inhaled Amikacin Versus Placebo to Prevent Ventilator Associated Pneumonia
The objective of the study is to prove that after the third day of invasive mechanical ventilation a three-day course of inhaled amikacin reduces the incidence of subsequent VAP.
Parallel two group double blind randomized controlled clinical trial. Individual randomization, performed on day 4 of invasive mechanical ventilation, will be stratified on centre in order to account for variations in VAP prevention bundle implementation and use of systemic antibiotics the day of randomization. Patients will be treated three consecutive days with inhaled amikacin or placebo. Patients will be followed up daily in the intensive care unit for the occurrence of VAP according to international guidelines until day 28.
- Conditions
- Pneumonia, Ventilator-Associated
- Being tested
- Inhaled amikacin, Inhaled placebo
- Keywords
- Prevention, inhaled amikacin, placebo
- Medical subject headings
- Pneumonia, Ventilator-Associated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Inhaled amikacinDrug
Once a day, inhaled amikacin at day 4, day 5 and day 6 of invasive mechanical ventilation: 20 mg/kg of ideal body weight, maximum 2 g per day.
Inhaled placeboDrug
Once a day, inhaled placebo at day 4, day 5 and day 6 of invasive mechanical ventilation.
| Study group | Role | What they receive |
|---|---|---|
| Inhaled amikacin | Experimental | Inhaled amikacin at day 4, day 5 and day 6 of invasive mechanical ventilation: 20 mg/kg of ideal body weight, maximum 2 g per day. Receives: Drug: Inhaled amikacin |
| Placebo | Placebo comparator | Once a day, inhaled placebo at day 4, day 5 and day 6 of invasive mechanical ventilation. Receives: Drug: Inhaled placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of a first VAP episode from randomization to day 28
Measured: Patients will be followed from randomization to day 28
Secondary outcomes (18)
Incidence of a first VAP episode in the subgroups of patients with tracheobronchial colonization or tracheobronchitis
Measured: At randomization
Incidence of VAP due to Gram negative amikacin sensitive bacteria
Measured: Patients will be followed from randomization to day 28
Clinical pulmonary infection score evolution
Measured: Patients will be followed from randomization to day 28
Ventilator associated events incidence
Measured: Patients will be followed from randomization to day 28
Number of systemic antibiotics administered per day
Measured: Patients will be followed from randomization to day 28
Number of days with at least one administration of a systemic antibiotic
Measured: Patients will be followed from randomization to day 28
Incidence of antibiotic resistant bacteria isolated on clinical and hygiene samples
Measured: Patients will be followed from randomization to day 28
Incidence of acute kidney injury
Measured: Patients will be followed from randomization to day 28
Days spent on mechanical ventilation from randomization to day 90
Measured: Patients will be followed from randomization to day 90
Days from randomization to the first successful spontaneous breathing trial
Measured: Days from randomization to day 90 max
Days spent in the intensive care unit and in the hospital
Measured: Patients will be followed from randomization to discharge (day 90 max)
Day 90 mortality
Measured: Day 90
Incidence of bacteria producing extended spectrum beta-lactamase or high level derepressed celphalosporinase, of vancomycin resistant Enterococcus Sp. on rectal samples
Measured: Day 28
Relative bacterial species composition of respiratory and digestive microbiota
Measured: Patients will be followed from randomization to day 28
Maximum serum Concentration
Measured: Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24
Maximum sputum Concentration
Measured: Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24
Area Under the Curve
Measured: Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24
To evaluate the effects on respiratory mechanics of nebulization of amikacin by evaluating the benefit balance / risk
benefit : Improvement of respiratory mechanics by pharmacological effect risk : Degradation of respiratory mechanics by bronchospastic secondary effect, drug deposition in the intubation probe
Measured: Measurements at 8 hours, 12 hours and 24 hours after the end of nebulization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2017
- Study start19 Jul 2017
- Primary completion9 Mar 2021
- Study completion17 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pneumonia, Ventilator-AssociatedStudies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 850 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stephan EHRMANN, MD-PhD, Principal investigator, University Hospital, Tours
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03149640
- Sponsor's protocol ID
- PHRN15-SE / AMIKINHAL
- Acronym
- AMIKINHAL
- Status last verified
- Nov 2022
- First submitted
- 2 May 2017
- Last updated
- 22 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tavernier E, Barbier F, Meziani F, Quenot JP, Herbrecht JE, Landais M, Roux D, Seguin P, Schnell D, Veinstein A, Veber B, Lasocki S, Lu Q, Beduneau G, Ferrandiere M, Dahyot-Fizelier C, Plantefeve G, Nay MA, Merdji H, Andreu P, Vecellio L, Muller G, Cabrera M, Le Pennec D, Respaud R, Lanotte P, Gregoire N, Leclerc M, Helms J, Boulain T, Lacherade JC, Ehrmann S; REVA network and the CRICS-TRIGGESEP F-CRIN network. Inhaled amikacin versus placebo to prevent ventilator-associated pneumonia: the AMIKINHAL double-blind multicentre randomised controlled trial protocol. BMJ Open. 2021 Sep 14;11(9):e048591. doi: 10.1136/bmjopen-2020-048591.
PubMed 34521664Ehrmann S, Barbier F, Demiselle J, Quenot JP, Herbrecht JE, Roux D, Lacherade JC, Landais M, Seguin P, Schnell D, Veinstein A, Gouin P, Lasocki S, Lu Q, Beduneau G, Ferrandiere M, Plantefeve G, Dahyot-Fizelier C, Chebib N, Mercier E, Heuze-Vourc'h N, Respaud R, Gregoire N, Garot D, Nay MA, Meziani F, Andreu P, Clere-Jehl R, Zucman N, Azais MA, Saint-Martin M, Gandonniere CS, Benzekri D, Merdji H, Tavernier E; Reva and CRICS-TRIGGERSEP F-CRIN Research Networks. Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia. N Engl J Med. 2023 Nov 30;389(22):2052-2062. doi: 10.1056/NEJMoa2310307. Epub 2023 Oct 25.
PubMed 37888914
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-blinded Multicenter Randomized Controlled Trial Comparing Inhaled Amikacin Versus Placebo to Prevent Ventilator Associated Pneumonia
- ClinicalTrials.gov ID
- NCT03149640
- Acronym / sponsor ID
- AMIKINHAL / PHRN15-SE / AMIKINHAL
- Conditions
- Pneumonia, Ventilator-Associated
- Keywords
- Prevention, inhaled amikacin, placebo
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 850 participants (actual)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Study start
- 19 Jul 2017 (actual)
- Primary completion
- 9 Mar 2021 (actual)
- Study completion
- 17 Jun 2021 (actual)
- First posted
- 11 May 2017 (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.
The objective of the study is to prove that after the third day of invasive mechanical ventilation a three-day course of inhaled amikacin reduces the incidence of subsequent VAP.
Parallel two group double blind randomized controlled clinical trial. Individual randomization, performed on day 4 of invasive mechanical ventilation, will be stratified on centre in order to account for variations in VAP prevention bundle implementation and use of systemic antibiotics the day of randomization. Patients will be treated three consecutive days with inhaled amikacin or placebo. Patients will be followed up daily in the intensive care unit for the occurrence of VAP according to international guidelines until day 28.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Inhaled amikacin | Experimental | Drug: Inhaled amikacinInhaled amikacin at day 4, day 5 and day 6 of invasive mechanical ventilation: 20 mg/kg of ideal body weight, maximum 2 g per day. |
| Placebo | Placebo comparator | Drug: Inhaled placeboOnce a day, inhaled placebo at day 4, day 5 and day 6 of invasive mechanical ventilation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 18 years the day of inclusion
- Mechanical ventilation through an endotracheal tube for more than three consecutive days (72h)
- Written informed consent of the patient or a proxy
- Patients covered by or having the rights to French social security
- Negative pregnancy test, at the time of inclusion, in women of childbearing potential
Key exclusion criteria (12 listed)
- Suspicion or confirmed VAP the day of inclusion
- Clinical indication for systemic aminoglycoside therapy the day of inclusion : as deemed necessary by the clinician in charge
- Stage 2 or 3 KDIGO* classification acute kidney injury the day of inclusion excepted in patients undergoing renal replacement therapy
- Chronic kidney failure : baseline glomerular filtration lower than 30 mL/min
- Patient scheduled for extubation within the next 24h
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 |
|---|---|---|
| Inhaled amikacinOnce a day, inhaled amikacin at day 4, day 5 and day 6 of invasive mechanical ventilation: 20 mg/kg of ideal body weight, maximum 2 g per day. | Drug | Inhaled amikacin |
| Inhaled placeboOnce a day, inhaled placebo at day 4, day 5 and day 6 of invasive mechanical ventilation. | Drug | Placebo |
Primary outcome
Incidence of a first VAP episode from randomization to day 28
Time frame: Patients will be followed from randomization to day 28
18 secondary outcomes
Incidence of a first VAP episode in the subgroups of patients with tracheobronchial colonization or tracheobronchitis
Time frame: At randomization
Incidence of VAP due to Gram negative amikacin sensitive bacteria
Time frame: Patients will be followed from randomization to day 28
Clinical pulmonary infection score evolution
Time frame: Patients will be followed from randomization to day 28
Ventilator associated events incidence
Time frame: Patients will be followed from randomization to day 28
Number of systemic antibiotics administered per day
Time frame: Patients will be followed from randomization to day 28
Number of days with at least one administration of a systemic antibiotic
Time frame: Patients will be followed from randomization to day 28
Incidence of antibiotic resistant bacteria isolated on clinical and hygiene samples
Time frame: Patients will be followed from randomization to day 28
Incidence of acute kidney injury
Time frame: Patients will be followed from randomization to day 28
Days spent on mechanical ventilation from randomization to day 90
Time frame: Patients will be followed from randomization to day 90
Days from randomization to the first successful spontaneous breathing trial
Time frame: Days from randomization to day 90 max
Days spent in the intensive care unit and in the hospital
Time frame: Patients will be followed from randomization to discharge (day 90 max)
Day 90 mortality
Time frame: Day 90
Incidence of bacteria producing extended spectrum beta-lactamase or high level derepressed celphalosporinase, of vancomycin resistant Enterococcus Sp. on rectal samples
Time frame: Day 28
Relative bacterial species composition of respiratory and digestive microbiota
Time frame: Patients will be followed from randomization to day 28
Maximum serum Concentration
Time frame: Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24
Maximum sputum Concentration
Time frame: Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24
Area Under the Curve
Time frame: Between Hour 0-Hour 8, between Hour 8-Hour 16 and between Hour 16-Hour 24
To evaluate the effects on respiratory mechanics of nebulization of amikacin by evaluating the benefit balance / risk
Time frame: Measurements at 8 hours, 12 hours and 24 hours after the end of nebulization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2025.
- Results publication: PubMed 34521664Tavernier E, Barbier F, Meziani F, Quenot JP, Herbrecht JE, Landais M, Roux D, Seguin P, Schnell D, Veinstein A, Veber B, Lasocki S, Lu Q, Beduneau G, Ferrandiere M, Dahyot-Fizelier C, Plantefeve G, Nay MA, Merdji H, Andreu P, Vecellio L, Muller G, Cabrera M, Le Pennec D, Respaud R, Lanotte P, Gregoire N, Leclerc M, Helms J, Boulain T, Lacherade JC, Ehrmann S; REVA network and the CRICS-TRIGGESEP F-CRIN network. Inhaled amikacin versus placebo to prevent ventilator-associated pneumonia: the AMIKINHAL double-blind multicentre randomised controlled trial protocol. BMJ Open. 2021 Sep 14;11(9):e048591. doi: 10.1136/bmjopen-2020-048591.
- Derived from this study: PubMed 37888914Ehrmann S, Barbier F, Demiselle J, Quenot JP, Herbrecht JE, Roux D, Lacherade JC, Landais M, Seguin P, Schnell D, Veinstein A, Gouin P, Lasocki S, Lu Q, Beduneau G, Ferrandiere M, Plantefeve G, Dahyot-Fizelier C, Chebib N, Mercier E, Heuze-Vourc'h N, Respaud R, Gregoire N, Garot D, Nay MA, Meziani F, Andreu P, Clere-Jehl R, Zucman N, Azais MA, Saint-Martin M, Gandonniere CS, Benzekri D, Merdji H, Tavernier E; Reva and CRICS-TRIGGERSEP F-CRIN Research Networks. Inhaled Amikacin to Prevent Ventilator-Associated Pneumonia. N Engl J Med. 2023 Nov 30;389(22):2052-2062. doi: 10.1056/NEJMoa2310307. Epub 2023 Oct 25.
- 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. This study is not recruiting at the moment.
Stephan EHRMANN, MD-PhD principal investigator
University Hospital, Tours
18 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 Inhaled amikacin in people with Pneumonia, Ventilator-Associated, run by University Hospital, Tours at 18 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 5 inclusion and 12 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: finished, as of the sponsor's last update on 22 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of a first VAP episode from randomization to day 28 (time frame: Patients will be followed from randomization to day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03149640, which also lists 2 linked publications.
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 22 Dec 2025.