Compare Ceftazidime-Avibactam and Doripenem Followed by Oral Therapy for Hospitalized Adults With Complicated UTIs (Urinary Tract Infections)
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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.
Condition | Intervention | Phase |
---|---|---|
cUTI Complicated Urinary Tract Infection Acute Pyelonephritis |
Drug: CAZ-AVI Drug: Doripenem Drug: Either 500 mg of Ciprofloxacin (oral) Drug: or 800 mg/160 mg of sulfamethoxazole/trimethoprim |
Phase 3 |
Study Type: | Interventional |
Study Design: | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
Official Title: | 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 |
- The proportion of patients with resolved (or return to premorbid) UTI (Urinary Track Infection) symptoms except flank pain and resolution or improvement in flank pain based on patient-reported symptom assessment response [ Time Frame: Day 5 after study drug start ] [ Designated as safety issue: No ]
- The proportion of patients with a per patient microbiological eradication and resolution (or return to premorbid) of all UTI (Urinary Track Infection)-specified symptoms based on patient-reported symptom assessment response [ Time Frame: 21 to 25 day after randomization ] [ Designated as safety issue: No ]
- The proportion of patients with a favorable per patient microbiological response in the microbiological modified Intent-To-Treat analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after study drug start ] [ Designated as safety issue: No ]
- The proportion of patients with a favorable per patient microbiological response in the microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after study drug start ] [ Designated as safety issue: No ]
- The proportion of patients with a favorable per patient microbiological response in the extended microbiological evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after study drug start ] [ Designated as safety issue: No ]
- The proportion of patients with resolution (or return to premorbid) of all UTI (Urinary Track Infection)-specific symptoms based on the patient-reported symptom assessment response in the microbiological modified Intent-To-Treat analysis set [ Time Frame: 21 to 25 days and 45 to 52 days after study drug start ] [ Designated as safety issue: No ]
- The proportion of favorable per-pathogen microbiological response in the microbiological modified Intent-To-Treat analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after study drug start ] [ Designated as safety issue: No ]
- The proportion of favorable per-pathogen microbiological response in the microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
- The proportion of favorable per-pathogen microbiological response in the extended microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
- The proportion of patients with an investigator-determined clinical cure in the microbiological modified Intent-To-Treat analysis set [ Time Frame: Within 24 hours after IV(intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
- The proportion of patients with an investigator-determined clinical cure in the microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
- The proportion of patients with an investigator-determined clinical cure in the extended microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion,anytime between 21 - 25 days and anytime between 45 - 52 days after the start of the study drug ] [ Designated as safety issue: No ]
- The proportion of patients with an investigator-determined clinical cure in the clinically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
- The favorable per pathogen microbiologic response by categories of minimum inhibitory concentration in the microbiological modified Intent-To-Treat analysis set [ Time Frame: Within 24 hours after IV(intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
- The favorable per pathogen microbiologic response by categories of minimum inhibitory concentration in the microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
- The favorable per pathogen microbiologic response by categories of minimum inhibitory concentration in the extended microbiologically evaluable analysis set [ Time Frame: Within 24 hours after completion of study drug, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
- The proportion of patients with favorable investigator clinical response assessment in patients infected with a ceftazidime resistant pathogen in the microbiological modified Intent-To-Treat analysis set [ Time Frame: 21 to 25 days after study drug start ] [ Designated as safety issue: No ]
- The proportion of patients with an investigator-determined clinical cure in patients infected with a ceftazidime resistant pathogen in the microbiologically evaluable analysis set [ Time Frame: 21 to 25 days after study drug start ] [ Designated as safety issue: No ]
- The proportion of patients with an investigator-determined clinical cure in patients infected with a ceftazidime resistant pathogen in the extended microbiologically evaluable analysis set [ Time Frame: 21 to 25 days after study drug start ] [ Designated as safety issue: No ]
- The proportion of patients with favorable per-patient microbiological response for patients infected with a ceftazidime resistant pathogen in the microbiological modified Intent-To-Treat analysis set [ Time Frame: 21 to 25 days after study drug start ] [ Designated as safety issue: No ]
- The proportion of patients with favorable per-patient microbiological response for patients infected with a ceftazidime resistant pathogen in the microbiologically evaluable analysis set [ Time Frame: 21 to 25 days after study drug start ] [ Designated as safety issue: No ]
- The proportion of patients with favorable per-patient microbiological response for patients infected with a ceftazidime resistant pathogen in the extended microbiologically evaluable analysis set [ Time Frame: 21 to 25 days after study drug start ] [ Designated as safety issue: No ]
- The proportion of patients with symptomatic resolution (defined in the primary variables) for patients infected with a ceftazidime resistant pathogen in the microbiological modified Intent-To-Treat analysis set [ Time Frame: Day 5 and 21 to 25 days after study drug start ] [ Designated as safety issue: No ]
- The time to first defervescence while on IV (intravenous) study therapy in patients in the microbiological modified Intent-To-Treat analysis set who have fever at study entry [ Time Frame: Any time after start of study drug to end of IV (intravenous) study therapy, which is a minimum of 5 days to a maximum of 14 days of IV study therapy ] [ Designated as safety issue: No ]
- The time to first defervescence while on IV (intravenous) study therapy in patients in the microbiologically evaluable analysis set who have fever at study entry [ Time Frame: Any time after start of study drug to end of IV (intravenous) study therapy, which is a minimum of 5 days to a maximum of 14 days of IV study therapy ] [ Designated as safety issue: No ]
- The time to first defervescence while on IV (intravenous) study therapy in patients in the clinically evaluable analysis set who have fever at study entry [ Time Frame: Any time after start of study drug to end of IV (intravenous) study therapy, which is a minimum of 5 days to a maximum of 14 days of IV study therapy ] [ Designated as safety issue: No ]
- Profile of pharmacokinetic (PK) of the individual components of CAZ-AVI (avibactam and ceftazidime)- maximum plasma concentration (Cmax) [ Time Frame: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug ] [ Designated as safety issue: No ]Cmax - Maximum plasma concentration
- Profile of pharmacokinetic (PK) of the individual components of CAZ-AVI (avibactam and ceftazidime)- minimum plasma concentration (Cmin) [ Time Frame: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug ] [ Designated as safety issue: No ]Cmin - Minimum plasma concentration
- Profile of pharmacokinetic (PK) of the individual components of CAZ-AVI (avibactam and ceftazidime)- area under the plasma concentration time curve at steady state (AUCss) [ Time Frame: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug ] [ Designated as safety issue: No ]AUCss - Area under the plasma concentration time curve at steady state
- Profile of pharmacokinetic (PK) of the individual components of CAZ-AVI (avibactam and ceftazidime)- terminal half-life (t½ ) [ Time Frame: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug ] [ Designated as safety issue: No ]t½ - terminal half-life
- The time to first defervescence while on IV (intravenous) study therapy in patients in the extended microbiologically evaluable analysis set who have fever at study entry [ Time Frame: Any time after start of study drug to end of IV (intravenous) study therapy, which is a minimum of 5 days to a maximum of 14 days of IV study therapy ] [ Designated as safety issue: No ]
- The safety and tolerability by incidence and severity of adverse events and serious adverse events, vital signs, clinical laboratory tests, ECGs and physical exams [ Time Frame: study duration (from screening visit (Day -1) through last follow up visit (up to 52 days) ] [ Designated as safety issue: Yes ]
Estimated Enrollment: | 964 |
Study Start Date: | September 2012 |
Estimated Study Completion Date: | March 2014 |
Estimated Primary Completion Date: | March 2014 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
Experimental: AZ Drug
IV treatment
|
Drug: CAZ-AVI
Drug: Ceftazidime 2000 mg and 500 mg of avibactam Drug: 500 mg of Ciprofloxacin (oral) Drug: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral) Drug: Either 500 mg of Ciprofloxacin (oral)
Drug: or 800 mg/160 mg of sulfamethoxazole/trimethoprim
or 800 mg/160 mg of sulfamethoxazole/trimethoprim
|
Active Comparator: Comparator
IV treatment
|
Drug: Doripenem
Drug: 500 mg of Doripenem Drug: 500 mg of Ciprofloxacin (oral) Drug: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral) Drug: Either 500 mg of Ciprofloxacin (oral)
Drug: or 800 mg/160 mg of sulfamethoxazole/trimethoprim
or 800 mg/160 mg of sulfamethoxazole/trimethoprim
|
Detailed Description:
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
Ages Eligible for Study: | 18 Years to 90 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
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 and has a positive urine culture within 48 hours of enrollment containing >/=10 to the fifth CFU/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
Contact: AstraZeneca Clinical Study Information | 800-236-9933 | information.center@astrazeneca.com |
Contact: Annette Fisher | 1-919-456-4039 | Annette.Fisher@ppdi.com |
Show 90 Study Locations
Study Director: | Paul Newell, MBBS, MRCP | AstraZeneca |
No publications provided
Responsible Party: | AstraZeneca |
ClinicalTrials.gov Identifier: | NCT01599806 History of Changes |
Other Study ID Numbers: | D4280C00004, 2011-005722-21 |
Study First Received: | May 15, 2012 |
Last Updated: | October 11, 2012 |
Health Authority: | Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Brazil: National Health Surveillance Agency Bulgaria: Bulgarian Drug Agency Canada: Health Canada Croatia: Ministry of Health and Social Care Czech Republic: State Institute for Drug Control France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Greece: National Organization of Medicines Israel: Ministry of Health India: Drugs Controller General of India Italy: National Institute of Health Mexico: Federal Commission for Sanitary Risks Protection Peru: Ministry of Health Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Romania: National Medicines Agency Russia: Ministry of Health and Social Development of the Russian Federation South Korea: Korea Food and Drug Administration (KFDA) Spain: Spanish Agency of Medicines Taiwan : Food and Drug Administration Ukraine: State Pharmacological Center - Ministry of Health United States: Food and Drug Administration |
Keywords provided by AstraZeneca:
Ceftazidime Doripenem Ciprofloxacin sulfamethoxazole/trimethoprim |
Anti-Bacterial Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions |
Additional relevant MeSH terms:
Pyelonephritis Urinary Tract Infections Nephritis, Interstitial Nephritis Kidney Diseases Urologic Diseases Pyelitis Infection Anti-Infective Agents Ceftazidime Ciprofloxacin Sulfamethoxazole Trimethoprim |
Trimethoprim-Sulfamethoxazole Combination Therapeutic Uses Pharmacologic Actions Anti-Bacterial Agents Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Infective Agents, Urinary Renal Agents Antimalarials Antiprotozoal Agents Antiparasitic Agents Folic Acid Antagonists |
ClinicalTrials.gov processed this record on October 17, 2012