Ceftazidime-Avibactam Compared With Doripenem Followed by Oral Therapy for Hospitalized Adults With Complicated UTIs (Urinary Tract Infections)

NCT ID: NCT01595438

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

598 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-31

Study Completion Date

2014-08-31

Brief Summary

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The purpose of this study is to evaluate the effects of Ceftazidime Avibactam compared to Doripenem for treating hospitalized patients with complicated urinary tract infections, including acute pyelonephritis

Detailed Description

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A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults

Conditions

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Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis

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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Ceftazidime - Avibactam ( CAZ-AVI)

IV treatment

Group Type EXPERIMENTAL

Ceftazidime - Avibactam ( CAZ-AVI)

Intervention Type DRUG

Ceftazidime 2000 mg and 500 mg of avibactam. Patients randomized to receive CAZ-AVI will receive an infusion of CAZ-AVI (2000 mg ceftazidime and 500 mg avibactam) every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 120 minutes

Either switch to oral therapy: 500 mg of Ciprofloxacin (oral)

Intervention Type DRUG

Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement

or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral)

Intervention Type DRUG

Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement

Doripenem

IV treatment

Group Type ACTIVE_COMPARATOR

Doripenem

Intervention Type DRUG

500 mg of Doripenem. Patients randomized to receive Doripenem will receive an infusion of Doripenem 500 mg every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 60 minutes

Either switch to oral therapy: 500 mg of Ciprofloxacin (oral)

Intervention Type DRUG

Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement

or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral)

Intervention Type DRUG

Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement

Interventions

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Ceftazidime - Avibactam ( CAZ-AVI)

Ceftazidime 2000 mg and 500 mg of avibactam. Patients randomized to receive CAZ-AVI will receive an infusion of CAZ-AVI (2000 mg ceftazidime and 500 mg avibactam) every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 120 minutes

Intervention Type DRUG

Doripenem

500 mg of Doripenem. Patients randomized to receive Doripenem will receive an infusion of Doripenem 500 mg every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 60 minutes

Intervention Type DRUG

Either switch to oral therapy: 500 mg of Ciprofloxacin (oral)

Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement

Intervention Type DRUG

or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral)

Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 18 to 90 years of age inclusive
* Female patients can participate if they are surgically sterile or completed menopause or females capable of having children and agree not to attempt pregnancy while receiving IV study therapy and for a period of 7 days after
* Has pyuria with \>/= 10 WBCs (white blood cell) and has a positive urine culture within 48 hours of enrollment containing \>/=10 to the fifth CFU (colony forming unit ) /ml of a recognized uropathogen known to be susceptible to IV study therapy (CAZ-AVI and doripenem)
* Demonstrates either acute pyelonephritis or complicated lower UTI without pyelonephritis.

Exclusion Criteria

* Urine pathogen is a Gram-positive pathogen or a uropathogen resistant to CAZ-AVI or doripenem
* Patient's urine culture at study entry isolates more than 2 microorganisms regardless of colony count or patient has a confirmed fungal UTI
* Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant
* Patient is immunocompromised
* Patient is considered unlikely to survive the 6- to 8-week study period or has a rapidly progressive or terminal illness including septic shock which is associated with a high risk of mortality
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Forest Laboratories

INDUSTRY

Sponsor Role collaborator

Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paul Newell, MBBS, MRCP

Role: STUDY_DIRECTOR

AstraZeneca

Locations

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Research Site

Sylmar, California, United States

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Royal Oak, Michigan, United States

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Lima, Ohio, United States

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Corrientes, , Argentina

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Córdoba, , Argentina

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Mendoza, , Argentina

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Santa Fe, , Argentina

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Belo Horizonte, , Brazil

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Campinas/SP, , Brazil

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Salvador, , Brazil

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São José Do Rio Preto - SP, , Brazil

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São Paulo, , Brazil

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Vila Clementino, , Brazil

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Pleven, , Bulgaria

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Rousse, , Bulgaria

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Sofia, , Bulgaria

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Zagreb, , Croatia

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Kyjov, , Czechia

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Opava, , Czechia

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Jena, , Germany

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Wuppertal, , Germany

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Athens, , Greece

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Budapest, , Hungary

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Nagykanizsa, , Hungary

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Nyíregyháza, , Hungary

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Zalaegerszeg, , Hungary

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Jerusalem, , Israel

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Petah Tikva, , Israel

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Safed, , Israel

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Fukuoka, , Japan

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Koshigaya-shi, , Japan

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Kyoto, , Japan

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Nagoya, , Japan

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Nara, , Japan

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Ōita, , Japan

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Sendai, , Japan

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Sunto-gun, , Japan

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Tokushima, , Japan

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Ueda-shi, , Japan

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Utsunomiya, , Japan

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Guadalajara, Jalisco, , Mexico

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Inowrocław, , Poland

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Krakow, , Poland

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Warsaw, , Poland

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Lisbon, , Portugal

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Brasov, , Romania

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Bucharest, , Romania

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Cluj-Napoca, , Romania

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Craiova, , Romania

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Iași, , Romania

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Arkhangelsk, , Russia

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Krasnodar, , Russia

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Moscow, , Russia

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Novosibirsk, , Russia

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Penza, , Russia

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Rostov-on-Don, , Russia

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Saint Petersburg, , Russia

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Saratov, , Russia

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Vsevolozhsk, , Russia

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Belgrade, , Serbia

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Kragujevac, , Serbia

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Poprad, , Slovakia

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Prešov, , Slovakia

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Trnava, , Slovakia

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Žilina, , Slovakia

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Busan, , South Korea

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Seoul, , South Korea

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Wŏnju, , South Korea

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Chiayi City, , Taiwan

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Taipei, , Taiwan

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Diyarbakır, , Turkey (Türkiye)

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Cherkasy, , Ukraine

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Dnipropetrovsk, , Ukraine

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Kharkiv, , Ukraine

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Kyiv, , Ukraine

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Lviv, , Ukraine

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Mykolaiv, , Ukraine

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Odesa, , Ukraine

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Uzhhorod, , Ukraine

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Zaporizhzhya, , Ukraine

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Countries

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United States Argentina Brazil Bulgaria Croatia Czechia Germany Greece Hungary Israel Japan Mexico Poland Portugal Romania Russia Serbia Slovakia South Korea Taiwan Turkey (Türkiye) Ukraine

References

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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)

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)

Wagenlehner FM, Sobel JD, Newell P, Armstrong J, Huang X, Stone GG, Yates K, Gasink LB. Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program. Clin Infect Dis. 2016 Sep 15;63(6):754-762. doi: 10.1093/cid/ciw378. Epub 2016 Jun 16.

Reference Type DERIVED
PMID: 27313268 (View on PubMed)

Other Identifiers

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2011-005721-43

Identifier Type: -

Identifier Source: secondary_id

D4280C00002

Identifier Type: -

Identifier Source: org_study_id

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