Aerosolized Antibiotics in the Treatment of Ventilator Associated Pneumonia

NCT02478710 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: 6517
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if administering inhaled antibiotics directly into the lungs in conjunction with intravenous (IV) antibiotics leads to better outcomes and decreased recurrence of ventilator associated pneumonia (VAP) when compared to IV antibiotics alone.

Conditions

Pneumonia, Ventilator-Associated

Outcome Measures

Primary Outcomes (2)

• Recurrence of Pneumonia

  Recurrence after a second bronchoalveolar lavage (BAL) reveals at least one bacterial species growing at concentrations of greater than 10 to the fourth power organisms during the time period of 9-21 days after initiating therapy.

  9-21 days after initiating antibiotic therapy

• Persistence of Pneumonia

  Persistence will be defined as the need to continue antibiotic therapy for greater than 7 days. This is reported as the number of participants with persistence of pneumonia.

  8 days after initiation of therapy for pneumonia

Secondary Outcomes (7)

• Ventilator-free Days

  28 days

• Intensive Care Unit (ICU) -Free Days in 28 Days

  28 days

• 28-day ICU Mortality

  28 days

• Renal Insufficiency

  28 days

• Multiple Organ Dysfunction Score Calculated at Randomization and on Day 7 of Treatment

  7 days

Study Arms (2)

Aerosolized Placebo

PLACEBO COMPARATOR

Placebo tobramycin 0.5 mL 0.9% normal saline q.12h. Placebo vancomycin 0.5 mL 0.9% normal saline q.8h.

Drug: Aerosolized Placebo

Aerosolized Tobramycin or Vancomycin

EXPERIMENTAL

Aerosolized tobramycin 300 mg diluted in 5 mL 0.9% normal saline q.12h. Aerosolized vancomycin 125 mg diluted in 5 mL 0.9% normal saline q.8h.

Drug: Aerosolized Tobramycin or Vancomycin

Interventions

Aerosolized Tobramycin or Vancomycin DRUG

Tobramycin: 300 mg diluted in 5 mL of 0.9% normal saline q.12h. Vancomycin: 125 mg diluted in 5 mL 0.9% normal saline q.8h.

Also known as: Tobi, Tobrex; Vancocin

Aerosolized Tobramycin or Vancomycin

Aerosolized Placebo DRUG

Placebo tobramycin: 5 ml 0.9% normal saline q. 12h. Placebo vancomycin: 5m 0.9% normal saline q. 8 hr.

Also known as: Normal saline solution

Aerosolized Placebo

Eligibility Criteria

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

You may qualify if:

• Clinical Pulmonary Infection Score (CPIS) greater than or equal to 6
• Intubated greater than or equal to 48 hours
• Screened for possible eligibility
• Bronchoscopy and bronchoalveolar lavage (BAL) or combicath performed
• Started on empiric intravenous (IV) and inhaled antibiotics after BAL for suspected ventilator associated pneumonia (VAP)
• \> 104 Colony Forming Units (CFU) on BAL

You may not qualify if:

• \<18 years of age
• Pregnant
• Human Immunodeficiency Virus (HIV) or on chronic immunosuppressants
• Absolute Neutrophil Count \<1,000
• Allergy to vancomycin or tobramycin
• Anaphylaxis to penicillin
• Cystic Fibrosis
• Previous enrollment
• Creatinine \>2 mg/dl or doubled within the previous 72 hours

Sponsors & Collaborators

• Wright State University: lead

Study Sites (1)

Miami Valley Hospital

Dayton, Ohio, 45409, United States

Location

Related Publications (18)

• Klastersky J, Huysmans E, Weerts D, Hensgens C, Daneau D. Endotracheally administered gentamicin for the prevention of infections of the respiratory tract in patients with tracheostomy: a double-blind study. Chest. 1974 Jun;65(6):650-4. doi: 10.1378/chest.65.6.650. No abstract available.

  PMID: 4208908 BACKGROUND

• Hallal A, Cohn SM, Namias N, Habib F, Baracco G, Manning RJ, Crookes B, Schulman CI. Aerosolized tobramycin in the treatment of ventilator-associated pneumonia: a pilot study. Surg Infect (Larchmt). 2007 Feb;8(1):73-82. doi: 10.1089/sur.2006.051.

  PMID: 17381399 BACKGROUND

• Chastre J, Wolff M, Fagon JY, Chevret S, Thomas F, Wermert D, Clementi E, Gonzalez J, Jusserand D, Asfar P, Perrin D, Fieux F, Aubas S; PneumA Trial Group. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA. 2003 Nov 19;290(19):2588-98. doi: 10.1001/jama.290.19.2588.

  PMID: 14625336 BACKGROUND

• MacIntyre NR, Rubin BK. Respiratory therapies in the critical care setting. Should aerosolized antibiotics be administered to prevent or treat ventilator-associated pneumonia in patients who do not have cystic fibrosis? Respir Care. 2007 Apr;52(4):416-21; discussion 421-2.

  PMID: 17417976 BACKGROUND

• Drew RH, Dodds Ashley E, Benjamin DK Jr, Duane Davis R, Palmer SM, Perfect JR. Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients. Transplantation. 2004 Jan 27;77(2):232-7. doi: 10.1097/01.TP.0000101516.08327.A9.

  PMID: 14742987 BACKGROUND

• Wood GC, Boucher BA. Aerosolized antimicrobial therapy in acutely ill patients. Pharmacotherapy. 2000 Feb;20(2):166-81. doi: 10.1592/phco.20.3.166.34783.

  PMID: 10678295 BACKGROUND

• Drobnic ME, Sune P, Montoro JB, Ferrer A, Orriols R. Inhaled tobramycin in non-cystic fibrosis patients with bronchiectasis and chronic bronchial infection with Pseudomonas aeruginosa. Ann Pharmacother. 2005 Jan;39(1):39-44. doi: 10.1345/aph.1E099. Epub 2004 Nov 23.

  PMID: 15562142 BACKGROUND

• Palmer LB, Smaldone GC, Chen JJ, Baram D, Duan T, Monteforte M, Varela M, Tempone AK, O'Riordan T, Daroowalla F, Richman P. Aerosolized antibiotics and ventilator-associated tracheobronchitis in the intensive care unit. Crit Care Med. 2008 Jul;36(7):2008-13. doi: 10.1097/CCM.0b013e31817c0f9e.

  PMID: 18552684 BACKGROUND

• Ioannidou E, Siempos II, Falagas ME. Administration of antimicrobials via the respiratory tract for the treatment of patients with nosocomial pneumonia: a meta-analysis. J Antimicrob Chemother. 2007 Dec;60(6):1216-26. doi: 10.1093/jac/dkm385. Epub 2007 Oct 13.

  PMID: 17934205 BACKGROUND

• Claridge JA, Edwards NM, Swanson J, Fabian TC, Weinberg JA, Wood C, Croce MA. Aerosolized ceftazidime prophylaxis against ventilator-associated pneumonia in high-risk trauma patients: results of a double-blind randomized study. Surg Infect (Larchmt). 2007 Feb;8(1):83-90. doi: 10.1089/sur.2006.042.

  PMID: 17381400 BACKGROUND

• Klepser ME. Role of nebulized antibiotics for the treatment of respiratory infections. Curr Opin Infect Dis. 2004 Apr;17(2):109-12. doi: 10.1097/00001432-200404000-00007.

  PMID: 15021049 BACKGROUND

• Palmer LB, Smaldone GC, Simon SR, O'Riordan TG, Cuccia A. Aerosolized antibiotics in mechanically ventilated patients: delivery and response. Crit Care Med. 1998 Jan;26(1):31-9. doi: 10.1097/00003246-199801000-00013.

  PMID: 9428540 BACKGROUND

• Smaldone GC. Advances in aerosols: adult respiratory disease. J Aerosol Med. 2006 Spring;19(1):36-46. doi: 10.1089/jam.2006.19.36.

  PMID: 16551213 BACKGROUND

• Crowther Labiris NR, Holbrook AM, Chrystyn H, Macleod SM, Newhouse MT. Dry powder versus intravenous and nebulized gentamicin in cystic fibrosis and bronchiectasis. A pilot study. Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 1):1711-6. doi: 10.1164/ajrccm.160.5.9810080.

  PMID: 10556145 BACKGROUND

• Heinzl B, Eber E, Oberwaldner B, Haas G, Zach MS. Effects of inhaled gentamicin prophylaxis on acquisition of Pseudomonas aeruginosa in children with cystic fibrosis: a pilot study. Pediatr Pulmonol. 2002 Jan;33(1):32-7. doi: 10.1002/ppul.10019.

  PMID: 11747258 BACKGROUND

• Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985 Oct;13(10):818-29.

  PMID: 3928249 BACKGROUND

• Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995 Oct;23(10):1638-52. doi: 10.1097/00003246-199510000-00007.

  PMID: 7587228 BACKGROUND

• Pugin J, Auckenthaler R, Mili N, Janssens JP, Lew PD, Suter PM. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage fluid. Am Rev Respir Dis. 1991 May;143(5 Pt 1):1121-9. doi: 10.1164/ajrccm/143.5_Pt_1.1121.

  PMID: 2024824 BACKGROUND

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated

Interventions

Vancomycin; Tobramycin; Saline Solution

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

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins; Nebramycin; Kanamycin; Aminoglycosides; Glycosides; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

Data was not collected for the Secondary Outcomes.

Results Point of Contact

• Title: Director of Clinical Research
• Organization: Premier Health

jllader@premierhealth.com

19374747850

Study Officials

• John K. Bini, MD

  Wright State University

  PRINCIPAL INVESTIGATOR

• Priti Parikh, PhD

  Wright State University

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2015
• First Posted: June 23, 2015
• Study Start: June 1, 2015
• Primary Completion: February 1, 2017
• Study Completion: July 1, 2022
• Last Updated: May 31, 2023
• Results First Posted: May 22, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)