Phase 3
Completed N=1,033
Ceftazidime-Avibactam Compared With Doripenem Followed by Oral Therapy for Hospitalized Adults With Complicated UTIs (Urinary Tract Infections)
Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis
Source: ClinicalTrials.gov NCT01595438 ↗
Enrolled (actual)
1,033
Serious AEs
3.2%
Results posted
Mar 2016
Primary outcomePrimary: Patient-reported Symptomatic Response at Day 5 (mMITT Analysis Set): Non-inferiority Hypothesis Test — 276; 276; 103; 124 Participants
Summary
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
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Patient-reported Symptomatic Response at Day 5 (mMITT Analysis Set): Non-inferiority Hypothesis Test |
276; 276; 103; 124; 14; 17 | — |
| PRIMARY Combined Patient-reported Symptomatic and Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis Test |
280; 269; 81; 109; 32; 39 | — |
| PRIMARY Per-patient Microbiological Response at TOC (mMITT Analysis Set): Non-inferiority Hypothesis Test |
304; 296; 58; 83; 31; 38 | — |
| SECONDARY Per-patient Microbiological Response at EOT (IV) (mMITT Analysis Set) |
374; 395; 1; 3; 18; 19 | — |
| SECONDARY Per-patient Microbiological Response at LFU (mMITT Analysis Set) |
268; 254; 83; 125; 42; 38 | — |
| SECONDARY Per-patient Microbiological Response at EOT (IV) (ME at EOT (IV) Analysis Set) |
324; 359; 1; 2 | — |
| SECONDARY Per-patient Microbiological Response at TOC (ME at TOC Analysis Set) |
241; 225; 45; 73 | — |
| SECONDARY Per-patient Microbiological Response at LFU (ME at LFU Analysis Set) |
182; 166; 63; 96 | — |
| SECONDARY Per-patient Microbiological Response at EOT (IV) (Extended ME at EOT (IV) Analysis Set) |
335; 369; 1; 2 | — |
| SECONDARY Per-patient Microbiological Response at TOC (Extended ME at TOC Analysis Set) |
243; 236; 49; 75 | — |
| SECONDARY Per-patient Microbiological Response at LFU (Extended ME at LFU Analysis Set) |
184; 173; 67; 99 | — |
| SECONDARY Investigator Determined Clinical Response at EOT (IV) (mMITT Analysis Set) |
378; 407; 5; 5; 10; 5 | — |
| SECONDARY Investigator Determined Clinical Response at TOC (mMITT Analysis Set) |
355; 377; 11; 24; 27; 16 | — |
| SECONDARY Investigator Determined Clinical Response at LFU (mMITT Analysis Set) |
335; 350; 23; 39; 35; 28 | — |
| SECONDARY Investigator Determined Clinical Response at EOT (IV) (ME at EOT (IV) Analysis Set) |
318; 358; 4; 2; 3; 1 | — |
| SECONDARY Investigator Determined Clinical Response at TOC (ME at TOC Analysis Set) |
277; 285; 4; 13; 5; 0 | — |
| SECONDARY Investigator Determined Clinical Response at LFU (ME at LFU Analysis Set) |
226; 236; 15; 24; 4; 2 | — |
| SECONDARY Investigator Determined Clinical Response at EOT (IV) (Extended ME at EOT (IV) Analysis Set) |
327; 368; 4; 2; 5; 1 | — |
| SECONDARY Investigator Determined Clinical Response at TOC (Extended ME at TOC Analysis Set) |
283; 298; 4; 13; 5; 0 | — |
| SECONDARY Investigator Determined Clinical Response at LFU (Extended ME at LFU Analysis Set) |
232; 246; 15; 24; 4; 2 | — |
| SECONDARY Investigator Determined Clinical Response at EOT (IV) (CE at EOT (IV) Analysis Set) |
346; 387; 4; 4 | — |
| SECONDARY Investigator Determined Clinical Response at TOC (CE at TOC Analysis Set) |
289; 309; 8; 21 | — |
| SECONDARY Investigator Determined Clinical Response at LFU (CE at LFU Analysis Set) |
235; 254; 19; 33 | — |
| SECONDARY Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (mMITT Analysis Set) |
67; 75; 33; 31; 17; 28 | — |
| SECONDARY Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (ME at TOC Analysis Set) |
47; 55; 22; 25; 14; 22 | — |
| SECONDARY Investigator Determined Clinical Response at TOC for Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (Extended ME at TOC Analysis Set) |
50; 61; 22; 25; 15; 23 | — |
| SECONDARY Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (mMITT Analysis Set) |
47; 51; 19; 27; 9; 6 | — |
| SECONDARY Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (ME at TOC Analysis Set) |
35; 37; 13; 20 | — |
| SECONDARY Per-patient Microbiological Response at TOC in Patients Infected by Ceftazidime-resistant Gram-negative Pathogen (Extended ME at TOC Analysis Set) |
37; 41; 14; 22 | — |
| SECONDARY Time to First Defervescence While on IV Study Therapy (mMITT Analysis Set) |
157; 150; 155; 143; 2; 7 | 0.038 sig |
| SECONDARY Time to First Defervescence While on IV Study Therapy (ME at TOC Analysis Set) |
124; 108; 124; 105; 0; 3 | 0.129 |
| SECONDARY Time to First Defervescence While on IV Study Therapy (Extended ME at TOC Analysis Set) |
124; 111; 124; 108; 0; 3 | 0.080 |
| SECONDARY Time to First Defervescence While on IV Study Therapy (CE at TOC Analysis Set) |
123; 118; 122; 113; 1; 5 | 0.155 |
| SECONDARY Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (mMITT Analysis Set) |
280; 293; 41; 51; 16; 11 | — |
| SECONDARY Per-pathogen Microbiological Response at TOC for Baseline Pathogen (mMITT Analysis Set) |
229; 220; 33; 35; 16; 9 | — |
| SECONDARY Per-pathogen Microbiological Response at LFU for Baseline Pathogen (mMITT Analysis Set) |
198; 189; 32; 30; 16; 6 | — |
| SECONDARY Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (Extended ME at EOT (IV) Analysis Set) |
250; 274; 34; 48; 13; 11 | — |
| SECONDARY Per-pathogen Microbiological Response at TOC for Baseline Pathogen (Extended ME at TOC Analysis Set) |
180; 176; 26; 29; 14; 4 | — |
| SECONDARY Per-pathogen Microbiological Response at LFU for Baseline Pathogen (Extended ME at LFU Analysis Set) |
129; 131; 24; 19; 11; 1 | — |
| SECONDARY Per-pathogen Microbiological Response at EOT (IV) for Baseline Pathogen (ME at EOT (IV) Analysis Set) |
249; 270; 33; 47; 13; 11 | — |
| SECONDARY Per-pathogen Microbiological Response at TOC for Baseline Pathogen (ME at TOC Analysis Set) |
180; 171; 25; 28; 14; 4 | — |
| SECONDARY Per-pathogen Microbiological Response at LFU for Baseline Pathogen (ME at LFU Analysis Set) |
129; 127; 23; 18; 11; 1 | — |
| SECONDARY Per-pathogen Microbiological Response at EOT (IV) for Blood Only (mMITT Analysis Set) |
31; 28; 2; 2; 1; 0 | — |
| SECONDARY Per-pathogen Microbiological Response at TOC for Blood Only (mMITT Analysis Set) |
31; 28; 3; 2; 1; 0 | — |
| SECONDARY Per-pathogen Microbiological Response at LFU for Blood Only (mMITT Analysis Set) |
29; 27; 3; 2; 1; 0 | — |
| SECONDARY Per-pathogen Microbiological Response at EOT (IV) for Blood Only (Extended ME at EOT (IV) Analysis Set) |
26; 24; 1; 1; 1; 0 | — |
| SECONDARY Per-pathogen Microbiological Response at TOC for Blood Only (Extended ME at TOC Analysis Set) |
22; 20; 2; 2; 1; 0 | — |
| SECONDARY Per-pathogen Microbiological Response at LFU for Blood Only (Extended ME at LFU Analysis Set) |
19; 17; 2; 1; 1; 0 | — |
| SECONDARY Per-pathogen Microbiological Response at EOT (IV) for Blood Only (ME at EOT (IV) Analysis Set) |
26; 24; 1; 1; 1; 0 | — |
| SECONDARY Per-pathogen Microbiological Response at TOC for Blood Only (ME at TOC Analysis Set) |
22; 20; 2; 2; 1; 0 | — |
| SECONDARY Per-pathogen Microbiological Response at LFU for Blood Only (ME at LFU Analysis Set) |
19; 17; 2; 1; 1; 0 | — |
| SECONDARY Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (mMITT Analysis Set) |
3; 5; 8; 6; 24; 23 | — |
| SECONDARY Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (Extended ME at TOC Analysis Set) |
2; 4; 5; 5; 17; 17 | — |
| SECONDARY Per-pathogen Microbiological Response at TOC by CAZ AVI MIC for Baseline Pathogen (ME at TOC Analysis Set) |
2; 4; 5; 5; 17; 17 | — |
| SECONDARY Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (mMITT Analysis Set) |
1; 3; 127; 119; 89; 86 | — |
| SECONDARY Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (Extended ME at TOC Analysis Set) |
1; 1; 106; 95; 64; 70 | — |
| SECONDARY Per-pathogen Microbiological Response at TOC by Doripenem MIC for Baseline Pathogen (ME at TOC Analysis Set) |
1; 1; 106; 95; 64; 70 | — |
| SECONDARY Plasma Concentrations for Ceftazidime Within 15 Minutes Before/After Dose (PK Analysis Set) |
65481.2 | — |
| SECONDARY Plasma Concentrations for Ceftazidime Between 30 to 90 Minutes After Dose(PK Analysis Set) |
47575.1 | — |
| SECONDARY Plasma Concentrations for Ceftazidime Between 300 to 360 Minutes After Dose(PK Analysis Set) |
16959.6 | — |
| SECONDARY Plasma Concentrations for Avibactam Within 15 Minutes Before/After Dose (PK Analysis Set) |
9307.3 | — |
| SECONDARY Plasma Concentrations for Avibactam Between 30 to 90 Minutes After Dose(PK Analysis Set) |
6587.2 | — |
| SECONDARY Plasma Concentrations for Avibactam Between 300 to 360 Minutes After Dose(PK Analysis Set) |
1883.2 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT01595438). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.