check_circleStudy Completed

Pneumonia, bacterial

Inhaled Amikacin Solution BAY41-6551 as Adjunctive Therapy in the treatment of Gram-Negative Pneumonia

Trial purpose

To demonstrate that as adjunctive therapy to intravenous (IV) antibiotics, BAY 41-6551 400 mg (amikacin as free base) administered as an aerosol by the Pulmonary Drug Delivery System (PDDS) Clinical every 12 hours is safe and more effective than placebo (aerosolized normal saline) administered as an aerosol by the PDDS Clinical every 12 hours, in intubated and mechanically-ventilated patients with Gram-negative Pneumonia. The secondary endpoint objectives are to evaluate the superiority of aerosolized BAY 41-6551 versus aerosolized placebo in pneumonia-related mortality, the Early Clinical Response at Day 10, the days on ventilation, and the days in the intensive care unit (ICU).

Key Participants Requirements

Sex

Both

Age

18 - N/A
  • - Males and non-pregnant, non-lactating females, 18 years of age or older
    - Intubated and mechanically-ventilated
    - Diagnosis of pneumonia defined as presence of a new or progressive infiltrate(s) on chest radiograph
    - Presence of Gram-negative organism(s) by either Gram stain or culture of respiratory specimen, or suspected Gram-negative pathogen
    - Impaired oxygenation
    - Clinical Pulmonary Infection Score (CPIS) of at least 6
    - Presence of a multi-drug resistant (MDR) organism in a pre-therapy respiratory specimen OR at least two risk factors for MDR organisms
  • - History of hypersensitivity to amikacin or other aminoglycosides
    - Has received antibiotic therapy for Gram-negative pneumonia for greater than 48 hours at the time of randomization
    - Known or suspected bacteremia secondary to Staphylococcus aureus
    - A positive urine and/or serum beta-human Chorionic Gonadotropin pregnancy test
    - Patients with a serum creatinine > 2 mg/dL (177 µmol/L) [Exception: Patients with a serum creatinine > 2 mg/dL (177 umol/L) and being treated with continuous renal replacement therapy (Continuous Veno-Venous Hemodialysis and CVVHemoDiafiltration) or daily hemodialysis will receive the aerosol study drug treatment]
    - Has been on mechanical ventilation for > 28 days
    - Is participating in or has participated in other investigational interventional studies within the last 28 days prior to study treatment
    - The risk of rapidly fatal illness and death within 72 hrs, or any concomitant condition not related to ventilator-associated pneumonia that, in the opinion of the investigator, precludes completion of study evaluations and the course of therapy
    - Has an Acute Physiology and Chronic Health Evaluation (APACHE) II score < 10
    - Patients receiving veno-venous extracorporeal circulation membrane oxygenation (V-V ECMO)

Trial summary

Enrollment Goal
461
Trial Dates
April 2013 - April 2017
Phase
Phase 3
Could I Receive a placebo
Yes
Products
Amikacin Inhalation Solution (BAY41-6551)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Withdrawn
Mannheim, 68167, Germany
Withdrawn
Regensburg, 93053, Germany
Withdrawn
Berlin, 13353, Germany
Withdrawn
Rostock, 181057, Germany
Withdrawn
Köln, 50937, Germany
Withdrawn
Hannover, 30625, Germany
Withdrawn
Berlin, 10117, Germany
Withdrawn
Southampton, SO16 6YD, United Kingdom
Withdrawn
Toulouse, 31059, France
Completed
Nimes, 30029, France
Withdrawn
Angers Cedex, 49100, France
Completed
PARIS, 75877, France
Withdrawn
Saint Michel, 16470, France
Withdrawn
Krakow, 31-826, Poland
Withdrawn
Leipzig, 04289, Germany
Withdrawn
Frankfurt, 60590, Germany
Withdrawn
Tübingen, 72076, Germany
Withdrawn
München, 81545, Germany
Withdrawn
Dresden, 01307, Germany
Withdrawn
Halle, 06112, Germany
Withdrawn
Glasgow, G42 9TY, United Kingdom
Withdrawn
Leeds, LS9 7TF, United Kingdom
Withdrawn
London, SE1 7EH, United Kingdom
Withdrawn
Winchester, SO22 5DG, United Kingdom
Completed
Paris, 75651, France
Withdrawn
Limoges, 87042, France
Withdrawn
Villefranche Sur Saône Cedex, 69655, France
Withdrawn
Paris Cedex 04, 75181, France
Withdrawn
Szczecin, 71-252, Poland
Withdrawn
Warszawa, 02-005, Poland
Withdrawn
Ota-ku, 143-8541, Japan
Withdrawn
Sagamihara, 252-0375, Japan
Withdrawn
Matsumoto, 399-0021, Japan
Completed
Nagoya, 460-0001, Japan
Completed
Osaka, 540-0006, Japan
Withdrawn
Osaka, 558-8558, Japan
Withdrawn
Sakai, 591-8555, Japan
Completed
Himeji, 670-8520, Japan
Withdrawn
Hofu, 747-8511, Japan
Completed
Nagasaki, 852-8501, Japan
Completed
Barcelona, 08036, Spain
Completed
Getafe, 28905, Spain
Completed
Poitiers, 86021, France
Withdrawn
Colombes, 92701, France
Withdrawn
Argenteuil Cedex, 95107, France
Withdrawn
VESOUL, 70014, France
Withdrawn
Poznan, 60-479, Poland
Completed
Szczecin, 70-111, Poland
Withdrawn
Poznan, 60-355, Poland
Withdrawn
Lodz, 90-549, Poland
Withdrawn
Krakow, 31-503, Poland
Withdrawn
Bydgoszcz, 85-094, Poland
Withdrawn
Morioka, 020-8505, Japan
Withdrawn
Niigata, 950-1197, Japan
Withdrawn
Niigata, 951-8520, Japan
Withdrawn
Bunkyo-ku, 113-8655, Japan
Withdrawn
Barcelona, 08035, Spain
Completed
BRUXELLES - BRUSSEL, 1090, Belgium
Withdrawn
BRUXELLES - BRUSSEL, 1070, Belgium
Completed
GENT, 9000, Belgium
Withdrawn
AMSTERDAM, 1105 AZ, Netherlands
Withdrawn
UTRECHT, 3584 CX, Netherlands
Withdrawn
Hradec Kralove, 50005, Czech Republic
Withdrawn
Brno, 62500, Czech Republic
Withdrawn
Stara Zagora, 6000, Bulgaria
Withdrawn
Plovdiv, 4002, Bulgaria
Withdrawn
Sofia, 1709, Bulgaria
Withdrawn
Sofia, 1527, Bulgaria
Withdrawn
Sofia, 1606, Bulgaria
Withdrawn
Budapest, H-1204, Hungary
Withdrawn
Bunkyo-ku, 113-8519, Japan
Completed
Maebashi, 371-8511, Japan
Completed
Seto, 489-8642, Japan
Completed
Kyoto, 607-8062, Japan
Withdrawn
Kumamoto, 860-8556, Japan
Completed
Kumamoto, 860-0008, Japan
Completed
Madrid, 28040, Spain
Withdrawn
Barcelona, 08003, Spain
Withdrawn
Alicante, 03010, Spain
Withdrawn
Badalona, 08916, Spain
Withdrawn
AMSTERDAM, 1081 HV, Netherlands
Completed
ROTTERDAM, 3083 AN, Netherlands
Withdrawn
Praha, 150 06, Czech Republic
Withdrawn
Rousse, 7000, Bulgaria
Withdrawn
Veliko Turnovo, 5000, Bulgaria
Withdrawn
Vac, 2600, Hungary
Withdrawn
Budapest, 1134, Hungary
Withdrawn
Szekesfehervar, 8000, Hungary
Completed
Kistarcsa, 2143, Hungary
Completed
Mezourlo / Larissa, Greece
Completed
Haidari, 12462, Greece
Withdrawn
Novosibirsk, 630008, Russia
Withdrawn
Novosibirsk, 630051, Russia
Withdrawn
St. Petersburg, 196247, Russia
Withdrawn
Budapest, 1115, Hungary
Withdrawn
Miskolc, 3501, Hungary
Withdrawn
Budapest, 1145, Hungary
Withdrawn
Szeged, 6720, Hungary
Completed
Heraklion, 711 10, Greece
Completed
Larissa, 41221, Greece
Withdrawn
Alexandroupolis, 68100, Greece
Completed
Smolensk, 214018, Russia
Withdrawn
Moscow, 123060, Russia
Withdrawn
Moscow, 117049, Russia
Withdrawn
Bucharest, 050098, Romania
Withdrawn
Cluj-Napoca, 400006, Romania
Withdrawn
Singapore, Singapore
Withdrawn
Singapore, 529889, Singapore
Completed
NIJMEGEN, 6525 GA, Netherlands
Withdrawn
Milano, 20162, Italy
Withdrawn
Padova, 35128, Italy
Withdrawn
Novara, 28100, Italy
Withdrawn
Pavia, 27100, Italy
Withdrawn
Bergamo, 24127, Italy
Completed
CRETEIL, 94010, France
Completed
NICE CEDEX 3, 06202, France
Withdrawn
Holon, 5810001, Israel
Completed
Petah Tikva, 4941492, Israel
Completed
Haifa, 3109601, Israel
Withdrawn
Afula, 1834111, Israel
Completed
Ramat Gan, 5262000, Israel
Completed
Tel Aviv, 64239, Israel
Completed
L'Hospitalet de Llobregat, 08907, Spain
Completed
Terrassa, 08221, Spain
Completed
Valencia, 46026, Spain
Completed
Girona, 17007, Spain
Completed
Braga, 4710-243, Portugal
Withdrawn
Porto, 4099, Portugal
Completed
Porto, 4200-072, Portugal
Withdrawn
Tübingen, 72076, Germany
Withdrawn
Hannover, 30625, Germany
Withdrawn
Aachen, 52074, Germany
Completed
Lyon, 69003, France
Completed
PARIS, 75674, France
Completed
PARIS, 75014, France
Withdrawn
Itabashi-ku, 173-8606, Japan
Completed
Nagakute, 480-1195, Japan
Withdrawn
Okayama, 700-8505, Japan
Completed
Sasebo, 857-8511, Japan
Withdrawn
Nagoya, 454-8502, Japan
Completed
Vac, 2600, Hungary
Completed
Budapest, 1121, Hungary
Completed
Budapest, 1125, Hungary
Completed
YVOIR, 5530, Belgium
Withdrawn
Bern, 3010, Switzerland
Withdrawn
Genève, 1205, Switzerland
Completed
Kyiv, 01133, Ukraine
Withdrawn
Kiev, 03110, Ukraine
Completed
Poltava, 36011, Ukraine
Withdrawn
Lugansk, 91045, Ukraine
Completed
Kharkiv, 61018, Ukraine
Completed
Yaroslavl, 150003, Russia
Completed
ANTWERPEN, 2060, Belgium
Withdrawn
Barcelona, 08035, Spain
Withdrawn
Porto, 4200-319, Portugal
Withdrawn
NANCY, 54037, France
Completed
Madrid, 28034, Spain
Completed
BRUXELLES - BRUSSEL, 1200, Belgium
Completed
Vinnitsa, 21000, Ukraine
Completed
Beijing, 100020, China
Completed
Shenyang, 110001, China
Withdrawn
Shanghai, 200080, China
Withdrawn
Beijing, 100191, China
Completed
Guangzhou, 510120, China
Withdrawn
Beijing, 100020, China
Withdrawn
Suzhou, 215006, China
Completed
Fuzhou, 350025, China
Completed
Haikou, 570311, China
Withdrawn
Beijing, 100038, China
Completed
Beiing, 100048, China
Withdrawn
Beijing, 100044, China
Completed
Beijing, 100029, China
Completed
Beijing, 100088, China
Completed
Shanghai, 200003, China
Completed
Shanghai, 200040, China
Withdrawn
Guangzhou, China
Withdrawn
Guangzhou, 510515, China
Withdrawn
Chongqing, 400038, China
Withdrawn
Chongqing, 400042, China
Completed
Chongqing, 400010, China
Completed
Nanjing, 210029, China
Completed
Hangzhou, 310016, China
Completed
Shenyang, 110004, China
Withdrawn
Chengdu, China
Completed
Xi'an, 710032, China
Withdrawn
Wuhan, 430060, China
Completed
Wuhan, 430030, China
Completed
Jinan, China
Withdrawn
Changsha, 410011, China
Withdrawn
Changsha, 410013, China
Completed
Changsha, 410008, China
Completed
Changsha, China
Withdrawn
Fuzhou, China
Completed
Yinchuan, 750004, China
Withdrawn
ENSCHEDE, 7511 JX, Netherlands
Completed
Omura, 856-8562, Japan
Completed
Matsusaka, 515-8544, Japan
Completed
Izumisano, 598-8577, Japan
Completed
Osaka, 543-0035, Japan
Completed
Nakagun, 319-1113, Japan
Withdrawn
Nanning, 530021, China
Withdrawn
Beijing, China
Completed
Shimajiri-gun, 901-1193, Japan
Completed
Xi'an, 710032, China
Completed
Xi'an, 710032, China
Withdrawn
Chongqing, 400016, China
Completed
Urumchi, 830054, China
Completed
Haikou, China
Completed
Haikou, China
Completed
Changchun, 130021, China
Withdrawn
Changchun, 130021, China
Withdrawn
Qingdao, 266000, China
Completed
Shenzhen, China
Completed
Xi'an, 710061, China
Withdrawn
Shanghai, 200032, China
Completed
Chengdu, 610041, China
Completed
Beijing, 100020, China
Withdrawn
Qingdao, 266071, China
Completed
Beijing, 100853, China
Withdrawn
Yokohama, 230-8765, Japan
Withdrawn
Fukuoka, 811-0213, Japan
Withdrawn
Onga, 807-0051, Japan
Withdrawn
Baotou, 014010, China
Completed
Shanghai, 200092, China
Completed
Beijing, 100029, China
Completed
Tianjin, 300052, China
Completed
Beijing, 100029, China
Completed
BRUXELLES - BRUSSEL, 1070, Belgium
Completed
Ota, 373-8585, Japan
Withdrawn
Hirakata, 573-1191, Japan
Withdrawn
Moscow, 117997, Russia
Withdrawn
Yekaterinburg, 620109, Russia
Completed
Yekaterinburg, 620102, Russia
Completed
Mineola, 10065, United States
Completed
Miami, 33125, United States
Completed
Hazard, 41701, United States
Completed
Phoenix, 85008-4956, United States
Withdrawn
New York, 10029, United States
Completed
Birmingham, 35233, United States
Completed
Cincinnati, 45267-0769, United States
Withdrawn
Chicago, 60612, United States
Withdrawn
Chicago, 60611, United States
Completed
New York, 10065, United States
Withdrawn
Grand Blanc, 48439, United States
Withdrawn
Johnson City, 13790, United States
Completed
Cleveland, 44195, United States
Withdrawn
Charleston, 25304, United States
Completed
Greensboro, 27401, United States
Withdrawn
Porto Alegre, 90610-000, Brazil
Completed
New York, 10019, United States
Withdrawn
Memphis, 38163, United States
Completed
São José do Rio Preto, Brazil
Withdrawn
Porto Alegre, 90880-480, Brazil
Withdrawn
Lima, Peru
Withdrawn
Lima, LIMA 11, Peru
Withdrawn
Buenos Aires [Capital Federal], 1120, Argentina
Withdrawn
Porto Alegre, 90035-074, Brazil
Withdrawn
Porto Alegre, 90450 130, Brazil
Completed
Belo Horizonte, 30150 221, Brazil
Withdrawn
Curitiba, 80440-080, Brazil
Withdrawn
Lima, 31, Peru
Withdrawn
Lima, LIMA 1, Peru
Withdrawn
Sherbrooke, J1H 5N4, Canada
Completed
Toronto, M5T 2S8, Canada
Completed
Barranquilla, Colombia
Withdrawn
Houston, 77030, United States
Withdrawn
Englewood, 07631, United States
Withdrawn
Bogotá, Colombia
Withdrawn
Bogotá, Colombia
Completed
Cali, Colombia
Withdrawn
Sao Paulo, 04012-000, Brazil
Completed
Campinas, 13060904, Brazil
Completed
Brooklyn, 11215, United States
Withdrawn
Farmington, 06030, United States
Withdrawn
Sarasota, 34232, United States
Completed
Taipei, Taiwan
Completed
Oklahoma City, 73117, United States
Completed
Columbus, 43215, United States
Completed
Mobile, 36617, United States
Withdrawn
Knoxville, 37920, United States
Withdrawn
Augusta, 30909, United States
Completed
Muncie, 47303, United States
Completed
Charleston, 29425, United States
Completed
Danbury, 06810, United States
Completed
Las Vegas, 89109, United States
Completed
Hartford, 06102, United States
Withdrawn
San Antonio, 78229, United States
Completed
Springfield, 65803, United States
Withdrawn
Detroit, 48202, United States
Completed
Taipei, 11217, Taiwan
Completed
Tainan, 710, Taiwan
Withdrawn
Kaoshiung, 81346, Taiwan
Withdrawn
Hermosillo, 83000, Mexico
Completed
Monterrey, 64460, Mexico
Withdrawn
México D.F., 14080, Mexico
Withdrawn
Chihuahua, Chih., 31000, Mexico
Completed
Aguascalientes, 20000, Mexico
Completed
San Luis Potosí, 78240, Mexico
Completed
Guadalajara, 44340, Mexico
Withdrawn
Toluca, 50130, Mexico
Completed
México, D.F., 07760, Mexico
Completed
Blacktown, 2148, Australia
Withdrawn
Herston, 4029, Australia
Withdrawn
Footscray, 3011, Australia
Withdrawn
Richmond, 3122, Australia
Completed
Clayton, 3168, Australia
Withdrawn
Parkville, 3050, Australia
Withdrawn
Hobart, 7000, Australia
Completed
Seoul, 137-701, Korea, Republic Of
Withdrawn
Seoul, 152-703, Korea, Republic Of
Completed
Seoul, 136-705, Korea, Republic Of
Completed
Seoul, 138-736, Korea, Republic Of
Withdrawn
Wonju-si, 220-701, Korea, Republic Of
Withdrawn
Herston, 4029, Australia
Completed
Wollongong, 2500, Australia
Completed
Kaohsiung, 82445, Taiwan
Withdrawn
Stanford, 94305, United States
Withdrawn
Incheon, 21565, Korea, Republic Of
Completed
Ankara, 06100, Turkey
Withdrawn
Ankara, 06500, Turkey
Withdrawn
Istanbul, 34160, Turkey
Completed
Trabzon, 61080, Turkey
Withdrawn
Istanbul, 34-300, Turkey
Withdrawn
Izmir, 35040, Turkey
Withdrawn
Seoul, 120-752, Korea, Republic Of
Completed
Chiang Mai, 50200, Thailand
Completed
Khon Kaen, 40002, Thailand
Withdrawn
Portland, 04102, United States
Completed
Newark, 19713, United States
Withdrawn
Baltimore, 21201, United States
Withdrawn
San Diego, 92103-8896, United States
Completed
Atlanta, 30342, United States
Withdrawn
Miami, 33136, United States
Completed
Youngstown, 44501, United States
Withdrawn
Hradec Kralove, 500 05, Czech Republic
Withdrawn
Praha 5, 150 06, Czech Republic
Completed
Zlin, 762 75, Czech Republic
Completed
Praha 10, 100 34, Czech Republic
Withdrawn
Usti nad Labem, 401 13, Czech Republic
Withdrawn
Córdoba, 5000, Argentina
Withdrawn
Mendoza, 5500, Argentina
Withdrawn
Cordoba, 5000, Argentina
Withdrawn
Merlo, B1712FJN, Argentina
Withdrawn
Buenos Aires, C1181ACH, Argentina
Terminated
Barranquilla, Colombia
Withdrawn
Bogotá, Colombia
Withdrawn
Guadalajara, 44280, Mexico
Withdrawn
San Antonio, 78229-3900, United States
Withdrawn
Buffalo, 14215, United States
Withdrawn
Jacksonville, 32209, United States
Withdrawn
Denver, 80204, United States
Completed
Kalamazoo, 49007, United States
Withdrawn
Manila, Philippines
Completed
Quezon City, NCR 1100, Philippines
Completed
Quezon City, 1105, Philippines
Completed
Hollywood, 33021-5421, United States
Completed
Butte, 59701, United States
Completed
Cleveland, 44109-1998, United States
Withdrawn
Royal Oak, 48073, United States
Withdrawn
Adelaide, 5011, Australia
Completed
Ottawa, K1H 8L6, Canada
Completed
Kingston, Canada
Completed
Iowa City, 52242, United States
Withdrawn
Nashville, 37212, United States
Completed
Asheville, 28801, United States
Completed
Tampa, 33606-3508, United States
Withdrawn
Peoria, 61606, United States
Withdrawn
Indianapolis, 46202, United States
Withdrawn
Chicago, 60612, United States
Withdrawn
Middletown, 45005, United States
Completed
Springfield, 62702, United States
Completed
Quebec, G1V 4G5, Canada
Completed
St. Louis, 63110-1093, United States
Withdrawn
Ann Arbor, 48109-0330, United States
Completed
Montreal, H1T 2M4, Canada
Completed
New York, 10065, United States

Primary Outcome

  • Number of Participants Surviving Through LFU Visit
    The primary efficacy variable is Survival through the late follow-up (LFU) visit. Survival is achieved when the participant is alive through the LFU visit. No other factors are considered in the evaluation of survival.
    date_rangeTime Frame:
    Up to 28-32 days after start of study treatment

Secondary Outcome

  • Number of Adjudicated Pneumonia-Related Death Through LFU Visit
    Death through LFU visit was adjudicated as pneumonia-related or pneumonia-unrelated for participants in the amikacin inhale group and participants in the placebo group.
    date_rangeTime Frame:
    Up to 28-32 days after start of study treatment
  • Number of Participants with Early Clinical Response
    Early Clinical Response was determined by the following: 1. CPIS scoring at Days 3, 5, and 10 compared to baseline (a. On Day 3, CPIS increase from baseline by at least 2 points was considered a failure. b. On Day 5, CPIS decrease from baseline of at least 1 point was not a failure. CPIS of no change from baseline was considered a failure. Any CPIS increase from baseline was a failure. c. On Day 10, CPIS decrease from baseline of at least 2 points was not a failure. CPIS decrease of only 1 point is a failure. Clinical Pulmonary Infection Score of no change was considered a failure. Any CPIS increase from baseline was a failure). 2. All-cause mortality through EOT visit was a failure. 3. The development of empyema or lung abscess through the EOT visit was a failure.
    date_rangeTime Frame:
    Up to 10 days after start of study treatment
  • Number of Days on Mechanical Ventilation Through LFU Visit
    Number of days on mechanical ventilator was summarized by descriptive statistics. Duration was defined as the number of days from the date of first study drug through the LFU visit. For participants who lived through the LFU visit, the ventilation days were actual days on ventilation with a maximum value of 28 days. For participants who died after Day 28 but on or before their LFU visit, the days on ventilator was censored at 28 days. For participants who died or discontinued off ventilation, the number of days on ventilation was actual days on ventilation with a maximum value of 28 days. For participants who died or discontinued on ventilation, the number of days on ventilation was 28 days. Further analysis of the number of days on mechanical ventilator was to be performed with censoring at Day 28 for subset of participants on ventilation without censoring.
    date_rangeTime Frame:
    Up to 28-32 days after start of study treatment
  • Number of Days in the ICU Through LFU Visit
    Number of days in ICU was summarized by descriptive statistics. Duration was defined as the number of days from the date of first study drug through the LFU visit. For participants who lived in ICU through the LFU visit, the ICU days were actual days in ICU with a maximum value of 28 days. For participants who died after Day 28 but on or before their LFU visit, the days in ICU was censored at 28 days. For participants who died or discontinued in ICU, the number of days in ICU was 28 days. Further analysis of the number of days in ICU was to be performed with censoring at Day 28 for subset of participants on ventilation and without censoring.
    date_rangeTime Frame:
    Up to 28-32 days after start of study treatment

Trial design

A Prospective, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of BAY 41-6551 as Adjunctive Therapy in Intubated and Mechanically-Ventilated Patients with Gram-Negative Pneumonia
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
Double Blind
Assignment
Parallel Assignment
Trial Arms
2