A Study Comparing Ceftazidime-Avibactam Versus Meropenem in Hospitalized Adults With Nosocomial Pneumonia

NCT ID: NCT01808092

Last Updated: 2017-09-06

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

969 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-30

Study Completion Date

2016-01-31

Brief Summary

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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

Detailed Description

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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

Conditions

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Nosocomial Pneumonia (NP) Ventilator-associated Pneumonia (VAP)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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CAZ-AVI

Intra-Venous treatment

Group Type EXPERIMENTAL

ceftazidim-avibactam (CAZ-AVI, experimental product)

Intervention Type DRUG

2000mg ceftazidime plus 500mg avibactam

Meropenem

Intra-Venous treatment

Group Type ACTIVE_COMPARATOR

meropenem (active comparator)

Intervention Type DRUG

1000mg of Meropenem

Interventions

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ceftazidim-avibactam (CAZ-AVI, experimental product)

2000mg ceftazidime plus 500mg avibactam

Intervention Type DRUG

meropenem (active comparator)

1000mg of Meropenem

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 18 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Joseph Chow, MD, FIDSA

Role: STUDY_DIRECTOR

AstraZeneca

Locations

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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

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Countries

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Argentina Brazil Bulgaria China Czechia France Hungary India Italy Japan Latvia Mexico Peru Philippines Poland Romania Russia Slovenia South Africa South Korea Spain Taiwan Turkey (Türkiye) Ukraine United Kingdom Vietnam

References

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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.

Reference Type DERIVED
PMID: 37700689 (View on PubMed)

Cheng 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.

Reference Type DERIVED
PMID: 32602065 (View on PubMed)

Tichy 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.

Reference Type DERIVED
PMID: 32349879 (View on PubMed)

Stone 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.

Reference Type DERIVED
PMID: 32071051 (View on PubMed)

Li 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.

Reference Type DERIVED
PMID: 30221827 (View on PubMed)

Nichols 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.

Reference Type DERIVED
PMID: 30061279 (View on PubMed)

Stone 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.

Reference Type DERIVED
PMID: 29912399 (View on PubMed)

Torres 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.

Reference Type DERIVED
PMID: 29254862 (View on PubMed)

Other Identifiers

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D4281C00001

Identifier Type: -

Identifier Source: org_study_id

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