A Study Comparing Ceftazidime-Avibactam Versus Meropenem in Hospitalized Adults With Nosocomial Pneumonia
A Phase III, Randomized, Multicentre, Double-blind, Double-dummy, Parallel-group Comparative Study to Determine the Efficacy, Safety And Tolerability of Ceftazidime-Avibactam Versus Meropenem in the Treatment of Nosocomial Pneumonia Including Ventilator-Associated Pneumonia in Hospitalized Adults
1 other identifier
interventional
969
26 countries
123
Brief Summary
The purpose of the study is to evaluate the effects of Ceftazidime-Avibactam compared to Meropenem for treating hospitalized adults with nosocomial pneumonia including ventilator-associated pneumonia
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Apr 2013
Typical duration for phase_3
123 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 28, 2013
CompletedFirst Posted
Study publicly available on registry
March 11, 2013
CompletedStudy Start
First participant enrolled
April 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2016
CompletedResults Posted
Study results publicly available
February 3, 2017
CompletedSeptember 6, 2017
September 1, 2017
2.8 years
February 28, 2013
December 9, 2016
September 1, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Clinically Modified Intent-to-treat Analysis Set (Co-primary Analyses)
The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.
At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Clinically Evaluable at TOC Analysis Set (Co-primary Analyses)
The number of patients meeting the cure criteria: the patient was not a clinical failure at end of treatment and the patient is alive and all signs and symptoms of pneumonia have resolved or improved to an extent that no antibacterial therapy for Nosocomial Pneumonia was taken between end of treatment and test-of-cure inclusive.
At the test-of-cure (TOC) visit (Day 21 to 25)
Secondary Outcomes (47)
The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Microbiologically Modified Intent-to-treat Analysis Set
At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Extended Microbiologically Evaluable Analysis Set
At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With Clinical Cure at Test-of-cure (TOC) Visit in the Microbiologically Evaluable Analysis Set
At the test-of-cure (TOC) visit (Day 21 to 25)
The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Microbiologically Modified Intent-to-treat Analysis Set
Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
The Number of Patients With Clinical Cure at End of Treatment (EOT) Visit in Clinically Modified Intent-to-treat Analysis Set
Patients were followed after the last IV dose but no later than 24 hours after the last IV dose.
- +42 more secondary outcomes
Study Arms (2)
CAZ-AVI
EXPERIMENTALIntra-Venous treatment
Meropenem
ACTIVE COMPARATORIntra-Venous treatment
Interventions
2000mg ceftazidime plus 500mg avibactam
Eligibility Criteria
You may qualify if:
- to 90 years of age inclusive
- Females can participate if surgically sterile or completed menopause; if able to have children, must have negative serum pregnancy test, agree not to attempt pregnancy and use acceptable contraception while receiving study therapy and for 1 week after
- Onset of symptoms ≥ 48 hours after admission or \<7 days after discharge from an inpatient acute or chronic care facility
- New or worsening infiltrate on chest X-ray obtained within 48 hours prior to randomization
- At least 1 of the following systemic signs:Fever (temperature \>38 C) or hypothermia (rectal/core temperature \<35 C); White blood cell count \>10,000 cells/mm3, or White blood cell count \<4500 cells/mm3, or \>15% band forms.
You may not qualify if:
- Pulmonary disease that, in the investigator's judgment, would preclude evaluation of therapeutic response (e.g. lung cancer, active tuberculosis, cystic fibrosis, granulomatous disease, fungal pulmonary infection or recent pulmonary embolism).
- Patients with lung abscess, pleural empyema or post obstructive pneumonia.
- Patients with an estimated creatinine clearance \<16ml/min by Cockcroft Gault formula or patients expected to require haemodialysis or other renal support while on study therapy.
- Acute hepatitis in the prior 6 months, cirrhosis, acute hepatic failure or acute decompensation of chronic hepatic failure.
- Patients receiving hemodialysis or peritoneal dialysis.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (123)
Research Site
Buenos Aires, Argentina
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Córdoba, Argentina
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Florida, Argentina
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La Plata, Argentina
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Mendoza, Argentina
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Belo Horizonte, Brazil
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Campinas/SP, Brazil
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Curitiba, Brazil
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São José do Rio Preto, Brazil
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Burgas, Bulgaria
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Plovdiv, Bulgaria
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Rousse, Bulgaria
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Sofia, Bulgaria
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Beijing, China
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Changsha, China
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Chengdu, China
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Chongqing, China
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Guangzhou, China
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Haikou, China
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Hangzhou, China
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Jiangyin, China
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Nanchang, China
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Qingdao, China
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Sanya, China
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Shanghai, China
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Shenyang, China
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Shenzhen, China
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Suzhou, China
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Tianjin, China
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Xi'an, China
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Xiamen, China
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Yangzhou, China
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Zhanjiang, China
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Kolín, Czechia
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Kyjov, Czechia
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Praha 10, Prague, Czechia
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Limoges, France
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Nantes, France
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Paris, France
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Pierre-Bénite, France
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Poitiers, France
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Strasbourg, France
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Tours, France
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Budapest, Hungary
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Miskolc, Hungary
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Székesfehérvár, Hungary
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Veszprém, Hungary
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Bangalore, India
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Jaipur, India
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Lucknow, India
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Pune, India
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Varanasi, India
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Bologna, Italy
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Fukuoka, Japan
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Higashiibaraki-gun, Japan
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Ikeda-shi, Japan
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Itabashi-ku, Japan
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Izumo-shi, Japan
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Kagoshima, Japan
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Kawasaki-shi, Japan
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Kitakyushu-shi, Japan
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Kushiro, Japan
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Matsuyama, Japan
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Osaka, Japan
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Saga, Japan
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Sapporo, Japan
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Sasebo-shi, Japan
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Tsuchiura-shi, Japan
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Tsukubo-gun, Japan
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Uji-shi, Japan
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Uki-shi, Japan
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Yanai-shi, Japan
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Liepāja, Latvia
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Guadalajara, Mexico
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Monterrey, Mexico
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Cusco, Peru
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Lima, Peru
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Iloilo City, Philippines
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Quezon City, Philippines
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Bydgoszcz, Poland
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Chrzanów, Poland
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Lublin, Poland
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Olsztyn, Poland
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Proszowice, Poland
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Suwałki, Poland
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Łęczna, Poland
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Craiova, Romania
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Timișoara, Romania
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Arkhangelsk, Russia
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Chelyabinsk, Russia
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Moscow, Russia
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Saint Petersburg, Russia
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Smolensk, Russia
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Zelenograd, Russia
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Golnik, Slovenia
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Randburg, South Africa
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Ansan-si, South Korea
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Anyang-si, South Korea
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Incheon, South Korea
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Jinju, South Korea
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Seoul, South Korea
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Wŏnju, South Korea
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Barcelona, Spain
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Madrid, Spain
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Sabadell(Barcelona), Spain
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Terrassa (Barcelona), Spain
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Taichung, Taiwan
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Ankara, Turkey (Türkiye)
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Dnipropetrovsk, Ukraine
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Donetsk, Ukraine
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Ivano-Frankivsk, Ukraine
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Kharkiv, Ukraine
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Kyiv, Ukraine
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Mykolayiv, Ukraine
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Poltava, Ukraine
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Vinnytsia, Ukraine
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Birmingham, United Kingdom
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Blackpool, United Kingdom
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Guildford, United Kingdom
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Hull, United Kingdom
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Hanoi, Vietnam
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Ho Chi Minh City, Vietnam
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Hochiminh, Vietnam
Related Publications (8)
Torres A, Wible M, Tawadrous M, Irani P, Stone GG, Quintana A, Debabov D, Burroughs M, Bradford PA, Kollef M. Efficacy and safety of ceftazidime/avibactam in patients with infections caused by beta-lactamase-producing Gram-negative pathogens: a pooled analysis from the Phase 3 clinical trial programme. J Antimicrob Chemother. 2023 Nov 6;78(11):2672-2682. doi: 10.1093/jac/dkad280.
PMID: 37700689DERIVEDCheng K, Newell P, Chow JW, Broadhurst H, Wilson D, Yates K, Wardman A. Safety Profile of Ceftazidime-Avibactam: Pooled Data from the Adult Phase II and Phase III Clinical Trial Programme. Drug Saf. 2020 Aug;43(8):751-766. doi: 10.1007/s40264-020-00934-3.
PMID: 32602065DERIVEDTichy E, Torres A, Bassetti M, Kongnakorn T, Di Virgilio R, Irani P, Charbonneau C. Cost-effectiveness Comparison of Ceftazidime/Avibactam Versus Meropenem in the Empirical Treatment of Hospital-acquired Pneumonia, Including Ventilator-associated Pneumonia, in Italy. Clin Ther. 2020 May;42(5):802-817. doi: 10.1016/j.clinthera.2020.03.014. Epub 2020 Apr 27.
PMID: 32349879DERIVEDStone GG, Bradford PA, Tawadrous M, Taylor D, Cadatal MJ, Chen Z, Chow JW. In Vitro Activity of Ceftazidime-Avibactam against Isolates from Respiratory and Blood Specimens from Patients with Nosocomial Pneumonia, Including Ventilator-Associated Pneumonia, in a Phase 3 Clinical Trial. Antimicrob Agents Chemother. 2020 Apr 21;64(5):e02356-19. doi: 10.1128/AAC.02356-19. Print 2020 Apr 21.
PMID: 32071051DERIVEDLi J, Lovern M, Green ML, Chiu J, Zhou D, Comisar C, Xiong Y, Hing J, MacPherson M, Wright JG, Riccobene T, Carrothers TJ, Das S. Ceftazidime-Avibactam Population Pharmacokinetic Modeling and Pharmacodynamic Target Attainment Across Adult Indications and Patient Subgroups. Clin Transl Sci. 2019 Mar;12(2):151-163. doi: 10.1111/cts.12585. Epub 2018 Sep 28.
PMID: 30221827DERIVEDNichols WW, Stone GG, Newell P, Broadhurst H, Wardman A, MacPherson M, Yates K, Riccobene T, Critchley IA, Das S. Ceftazidime-Avibactam Susceptibility Breakpoints against Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2018 Oct 24;62(11):e02590-17. doi: 10.1128/AAC.02590-17. Print 2018 Nov.
PMID: 30061279DERIVEDStone GG, Newell P, Gasink LB, Broadhurst H, Wardman A, Yates K, Chen Z, Song J, Chow JW. Clinical activity of ceftazidime/avibactam against MDR Enterobacteriaceae and Pseudomonas aeruginosa: pooled data from the ceftazidime/avibactam Phase III clinical trial programme. J Antimicrob Chemother. 2018 Sep 1;73(9):2519-2523. doi: 10.1093/jac/dky204.
PMID: 29912399DERIVEDTorres A, Zhong N, Pachl J, Timsit JF, Kollef M, Chen Z, Song J, Taylor D, Laud PJ, Stone GG, Chow JW. Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): a randomised, double-blind, phase 3 non-inferiority trial. Lancet Infect Dis. 2018 Mar;18(3):285-295. doi: 10.1016/S1473-3099(17)30747-8. Epub 2017 Dec 16.
PMID: 29254862DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- David Wilson, Statistical Team Leader - Infection
- Organization
- AstraZeneca
Study Officials
- STUDY DIRECTOR
Joseph Chow, MD, FIDSA
AstraZeneca
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 28, 2013
First Posted
March 11, 2013
Study Start
April 1, 2013
Primary Completion
January 1, 2016
Study Completion
January 1, 2016
Last Updated
September 6, 2017
Results First Posted
February 3, 2017
Record last verified: 2017-09