Study Comparing Inhaled Amikacin Versus Placebo to Prevent Ventilator Associated Pneumonia

NCT03149640 | Completed Phase 3 DMC

• 1 other identifier: PHRN15-SE / AMIKINHAL
• Study Type: interventional
• Target: 850
• Locations: 1 country
• Sites: 18

Brief 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. 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

Keywords

Prevention; inhaled amikacin; placebo

Outcome Measures

Primary Outcomes (1)

• Incidence of a first VAP episode from randomization to day 28

  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

  At randomization

• Incidence of VAP due to Gram negative amikacin sensitive bacteria

  Patients will be followed from randomization to day 28

• Clinical pulmonary infection score evolution

  Patients will be followed from randomization to day 28

• Ventilator associated events incidence

  Patients will be followed from randomization to day 28

• Number of systemic antibiotics administered per day

  Patients will be followed from randomization to day 28

Study Arms (2)

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.

Drug: Inhaled amikacin

Placebo

PLACEBO COMPARATOR

Once a day, inhaled placebo at day 4, day 5 and day 6 of invasive mechanical ventilation.

Drug: Inhaled placebo

Interventions

Inhaled amikacin DRUG

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 amikacin

Inhaled placebo DRUG

Once a day, inhaled placebo at day 4, day 5 and day 6 of invasive mechanical ventilation.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Chronic kidney failure : baseline glomerular filtration lower than 30 mL/min
• Patient scheduled for extubation within the next 24h
• Patient ventilated through a tracheostomy
• Patients allergic to aminoglycosides
• Myasthenia gravis
• Patients previously included in this study

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (18)

Service de Réanimation Chirurgicale

Angers, 49933, France

Location

Service de Réanimation Médicale - CH d'Angoulême

Angoulême, 16959, France

Location

Service de Réanimation Polyvalente

Argenteuil, France

Location

Service de Réanimation Médicale - Hôpital Louis Mourier

Colombes, 92700, France

Location

Service de Réanimation

Dijon, 21079, France

Location

Service de Réanimation Médicale - CHD Les Oudairies

La Roche-sur-Yon, 85025, France

Location

Service de Réanimation

Le Mans, 72037, France

Location

Service de Réanimation Médicale - Hôpital La Croix-Rousse

Lyon, 69317, France

Location

Service de Réanimation Médicale

Orléans, 45100, France

Location

Service de Réanimation Médicale - Hôpital Pitié Salpêtrière

Paris, 75013, France

Location

Service de Réanimation Médicale - CHU La Milétrie

Poitiers, 86021, France

Location

Service de Réanimation Médicale

Poitiers, 86021, France

Location

Service de Réanimation Médicale - CHU Pontchaillou

Rennes, 35033, France

Location

Service de Réanimation Médicale - CHU Rouen

Rouen, 76031, France

Location

Service de Réanimation Médicale - Hôpital Charles Nicolle

Rouen, 76031, France

Location

Service de Réanimation - NHC

Strasbourg, 67091, France

Location

Service de Réanimation Médicale - Hôpital de Hautepierre

Strasbourg, 67098, France

Location

Service de Réanimation médicale, Hôpital Trousseau

Tours, 37044, France

Location

Related Publications (2)

• 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.

  PMID: 34521664 RESULT

• Ehrmann 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.

  PMID: 37888914 DERIVED

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Stephan EHRMANN, MD-PhD

  University Hospital, Tours

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2017
• First Posted: May 11, 2017
• Study Start: July 19, 2017
• Primary Completion: March 9, 2021
• Study Completion: June 17, 2021
• Last Updated: December 22, 2025

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (18)