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Ceftazidime-Avibactam for the Treatment of Infections Due to Ceftazidime Resistant Pathogens

NCT ID: NCT01644643

Last Updated: 2017-09-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

345 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-01-31

Study Completion Date

2014-09-30

Brief Summary

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To Evaluate the Effects of Ceftazidime-Avibactam and Best Available Therapy in patients with complicated urinary tract infections and complicated intra-abdominal infections.

Detailed Description

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An Open-Label, Randomized, Multicenter, Phase III Study of Ceftazidime Avibactam (CAZ-AVI, formerly CAZ104) and Best Available Therapy for the Treatment of Infections Due to Ceftazidime Resistant Gram Negative Pathogens

Conditions

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Complicated Urinary Tract Infection Complicated Intra-abdominal Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

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

Metronidazole

Intervention Type DRUG

Anti-infective, 500 mg (cIAI only) Patients randomized to receive CAZ-AVI for cIAI will also receive metronidazole (500 mg) administered by IV infusion in a volume of 100 mL at a constant rate over 60 minutes immediately following the CAZ-AVI infusion

Best Available Therapy

IV treatment

Group Type ACTIVE_COMPARATOR

Best Available Therapy

Intervention Type DRUG

Patients randomized to receive Best Available Therapy will receive the best available standard of care (SOC) anti-infective therapy for their infection administered in accord with approved local label recommendation

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

Best Available Therapy

Patients randomized to receive Best Available Therapy will receive the best available standard of care (SOC) anti-infective therapy for their infection administered in accord with approved local label recommendation

Intervention Type DRUG

Metronidazole

Anti-infective, 500 mg (cIAI only) Patients randomized to receive CAZ-AVI for cIAI will also receive metronidazole (500 mg) administered by IV infusion in a volume of 100 mL at a constant rate over 60 minutes immediately following the CAZ-AVI infusion

Intervention Type DRUG

Other Intervention Names

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Flagyl

Eligibility Criteria

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Inclusion Criteria

* Patient must be ≥18 and ≤90 years of age
* 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
* Patient has a ceftazidime-resistant Gram negative pathogen that was isolated from an appropriate culture within 5 days prior to study entry (ie, within 5 days prior to Screening; the study-qualifying culture), which was determined to be the causative agent of the entry infection

Exclusion Criteria

* Patient has an APACHE II score \>30 (cIAI patients only)
* Patient has an infection due to Gram negative pathogen that is unlikely to respond to CAZ-AVI treatment (eg, Acinetobacter spp., Stenotrophomonas spp.)
* Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant Patient is immunocompromised
* Patient has a rapidly progressive or terminal illness with a high risk of mortality due to any cause, including acute hepatic failure, respiratory failure or severe septic shock such that they are unlikely to survive the 4- to 5-week study period.
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

Shreveport, Louisiana, United States

Site Status

Research Site

Lima, Ohio, United States

Site Status

Research Site

El Talar, , Argentina

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La Plata, , Argentina

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Pazardzhik, , Bulgaria

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Pleven, , Bulgaria

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Rousse, , Bulgaria

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Sofia, , Bulgaria

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Varna, , Bulgaria

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Veliko Tarnovo, , Bulgaria

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Slavonski Brod, , Croatia

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Zagreb, , Croatia

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Prague, , Czechia

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Tours, , France

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Nazareth, , Israel

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Petah Tikva, , Israel

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Ramat Gan, , Israel

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Tel Aviv, , Israel

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Guadalajara, , Mexico

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Mexico City, , Mexico

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Cusco, , Peru

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Surco, , Peru

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Manila, , Philippines

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Szczecin, , Poland

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Bucharest, , Romania

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Irkutsk, , Russia

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Krasnodar, , Russia

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Novosibirsk, , Russia

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Penza, , Russia

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Saint Petersburg, , Russia

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Yaroslavl, , Russia

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Johannesburg, , South Africa

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Seoul, , South Korea

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Barcelona, , Spain

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Madrid, , Spain

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Ankara, , Turkey (Türkiye)

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Antalya, , Turkey (Türkiye)

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Diyarbakır, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Dnipropetrovsk, , Ukraine

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Kharkiv, , Ukraine

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Kyiv, , Ukraine

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Zaporizhzhya, , Ukraine

Site Status

Countries

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United States Argentina Bulgaria Croatia Czechia France Israel Mexico Peru Philippines Poland Romania Russia South Africa South Korea Spain Turkey (Türkiye) Ukraine

References

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Carmeli Y, Armstrong J, Laud PJ, Newell P, Stone G, Wardman A, Gasink LB. Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomised, pathogen-directed, phase 3 study. Lancet Infect Dis. 2016 Jun;16(6):661-673. doi: 10.1016/S1473-3099(16)30004-4. Epub 2016 Apr 20.

Reference Type BACKGROUND
PMID: 27107460 (View on PubMed)

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)

Mendes RE, Castanheira M, Woosley LN, Stone GG, Bradford PA, Flamm RK. Characterization of beta-Lactamase Content of Ceftazidime-Resistant Pathogens Recovered during the Pathogen-Directed Phase 3 REPRISE Trial for Ceftazidime-Avibactam: Correlation of Efficacy against beta-Lactamase Producers. Antimicrob Agents Chemother. 2019 May 24;63(6):e02655-18. doi: 10.1128/AAC.02655-18. Print 2019 Jun.

Reference Type DERIVED
PMID: 30910899 (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)

Stone GG, Bradford PA, Newell P, Wardman A. In Vitro Activity of Ceftazidime-Avibactam against Isolates in a Phase 3 Open-Label Clinical Trial for Complicated Intra-Abdominal and Urinary Tract Infections Caused by Ceftazidime-Nonsusceptible Gram-Negative Pathogens. Antimicrob Agents Chemother. 2017 Jan 24;61(2):e01820-16. doi: 10.1128/AAC.01820-16. Print 2017 Feb.

Reference Type DERIVED
PMID: 27872067 (View on PubMed)

Study Documents

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Document Type: Study Protocol

D4280C00006 Clinical Study Protocol

View Document

Document Type: Study Protocol

D4280C00006 Clinical Study Protocol Amendment 2 Redacted amended

View Document

Document Type: Study Protocol

D4280C00006 Clinical Study Protocol Amendment 3 Redacted amended

View Document

Other Identifiers

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2012-000726-21

Identifier Type: -

Identifier Source: secondary_id

D4280C00006

Identifier Type: -

Identifier Source: org_study_id