Trial Outcomes & Findings for Safety and Efficacy of ZTI-01 (IV Fosfomycin) vs Piperacillin/Tazobactam for Treatment cUTI/AP Infections (NCT NCT02753946)
NCT ID: NCT02753946
Last Updated: 2019-03-07
Results Overview
Clinical cure (resolution or significant improvement in signs and symptoms) and microbiologic eradication (baseline pathogen) in m-MITT population
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
465 participants
Primary outcome timeframe
TOC Visit (Day 19)
Results posted on
2019-03-07
Participant Flow
Patients diagnosed with cUTI/AP based on signs and symtoms requiring 7 days hospitalization (or up to 14 days in case of bacteremia). No oral switch is allowed in the study. Confirmatory microbiology data only available after randomization.
At least 30% of patients required a diagnosis of AP. Receipt of effective systemic antibiotic for \>24 hrs within 72-hr window before randomization exclusionary but receiving single dose of short-acting systemic antibiotic within 72 hrs of randomization permitted up to a max of 25% of the study enrollments.
Participant milestones
| Measure |
ZTI-01
6 g ZTI-01 (IV fosfomycin) intravenously administered every 8 hours (18g total daily dose for 7-14 calendar days)
ZTI-01: 6g ZTI-01 intravenous infusion TID q8 hours
|
Piperacillin Tazobactam
4.5 g piperacillin/tazobactam (4 g piperacillin/0.5 g tazobactam) intravenously administered every 8 hours (13.5g total daily dose for 7-14 calendar days)
Piperacillin-tazobactam: 4.5g piperacillin-tazobactam intravenous infusion TID q8 hours
|
|---|---|---|
|
Overall Study
STARTED
|
233
|
231
|
|
Overall Study
COMPLETED
|
219
|
222
|
|
Overall Study
NOT COMPLETED
|
14
|
9
|
Reasons for withdrawal
| Measure |
ZTI-01
6 g ZTI-01 (IV fosfomycin) intravenously administered every 8 hours (18g total daily dose for 7-14 calendar days)
ZTI-01: 6g ZTI-01 intravenous infusion TID q8 hours
|
Piperacillin Tazobactam
4.5 g piperacillin/tazobactam (4 g piperacillin/0.5 g tazobactam) intravenously administered every 8 hours (13.5g total daily dose for 7-14 calendar days)
Piperacillin-tazobactam: 4.5g piperacillin-tazobactam intravenous infusion TID q8 hours
|
|---|---|---|
|
Overall Study
Adverse Event
|
7
|
6
|
|
Overall Study
Withdrawal by Subject
|
6
|
1
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
|
Overall Study
Physician Decision
|
0
|
2
|
Baseline Characteristics
1 subject randomized discontinued prior to treatment
Baseline characteristics by cohort
| Measure |
ZTI-01
n=233 Participants
6 g ZTI-01 (IV fosfomycin) intravenously administered every 8 hours (18g total daily dose for 7-14 calendar days)
ZTI-01: 6g ZTI-01 intravenous infusion TID q8 hours
|
Piperacillin Tazobactam
n=232 Participants
4.5 g piperacillin/tazobactam (4 g piperacillin/0.5 g tazobactam) intravenously administered every 8 hours (13.5g total daily dose for 7-14 calendar days)
Piperacillin-tazobactam: 4.5g piperacillin-tazobactam intravenous infusion TID q8 hours
|
Total
n=465 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=233 Participants
|
0 Participants
n=232 Participants
|
0 Participants
n=465 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=233 Participants
|
0 Participants
n=232 Participants
|
0 Participants
n=465 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=233 Participants
|
0 Participants
n=232 Participants
|
0 Participants
n=465 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=233 Participants
|
0 Participants
n=232 Participants
|
0 Participants
n=465 Participants
|
|
Race (NIH/OMB)
White
|
233 Participants
n=233 Participants
|
232 Participants
n=232 Participants
|
465 Participants
n=465 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=233 Participants
|
0 Participants
n=232 Participants
|
0 Participants
n=465 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=233 Participants
|
0 Participants
n=232 Participants
|
0 Participants
n=465 Participants
|
|
Region of Enrollment
Romania
|
6 Participants
n=233 Participants
|
2 Participants
n=232 Participants
|
8 Participants
n=465 Participants
|
|
Region of Enrollment
Hungary
|
4 Participants
n=233 Participants
|
5 Participants
n=232 Participants
|
9 Participants
n=465 Participants
|
|
Region of Enrollment
United States
|
1 Participants
n=233 Participants
|
0 Participants
n=232 Participants
|
1 Participants
n=465 Participants
|
|
Region of Enrollment
Czechia
|
7 Participants
n=233 Participants
|
7 Participants
n=232 Participants
|
14 Participants
n=465 Participants
|
|
Region of Enrollment
Ukraine
|
71 Participants
n=233 Participants
|
73 Participants
n=232 Participants
|
144 Participants
n=465 Participants
|
|
Region of Enrollment
Belarus
|
39 Participants
n=233 Participants
|
31 Participants
n=232 Participants
|
70 Participants
n=465 Participants
|
|
Region of Enrollment
Russia
|
39 Participants
n=233 Participants
|
39 Participants
n=232 Participants
|
78 Participants
n=465 Participants
|
|
Region of Enrollment
Latvia
|
13 Participants
n=233 Participants
|
16 Participants
n=232 Participants
|
29 Participants
n=465 Participants
|
|
Region of Enrollment
Poland
|
10 Participants
n=233 Participants
|
12 Participants
n=232 Participants
|
22 Participants
n=465 Participants
|
|
Region of Enrollment
Georgia
|
11 Participants
n=233 Participants
|
14 Participants
n=232 Participants
|
25 Participants
n=465 Participants
|
|
Region of Enrollment
Slovakia
|
8 Participants
n=233 Participants
|
16 Participants
n=232 Participants
|
24 Participants
n=465 Participants
|
|
Region of Enrollment
Bulgaria
|
6 Participants
n=233 Participants
|
4 Participants
n=232 Participants
|
10 Participants
n=465 Participants
|
|
Region of Enrollment
Lithuania
|
6 Participants
n=233 Participants
|
7 Participants
n=232 Participants
|
13 Participants
n=465 Participants
|
|
Region of Enrollment
Croatia
|
5 Participants
n=233 Participants
|
3 Participants
n=232 Participants
|
8 Participants
n=465 Participants
|
|
Region of Enrollment
Estonia
|
7 Participants
n=233 Participants
|
3 Participants
n=232 Participants
|
10 Participants
n=465 Participants
|
|
BMI (kg/m^2)
|
25.81 kg/m2
STANDARD_DEVIATION 5.355 • n=233 Participants • 1 subject randomized discontinued prior to treatment
|
26.44 kg/m2
STANDARD_DEVIATION 6.167 • n=231 Participants • 1 subject randomized discontinued prior to treatment
|
26.12 kg/m2
STANDARD_DEVIATION 5.776 • n=464 Participants • 1 subject randomized discontinued prior to treatment
|
|
Screening Creatinine Clearance Group
<20 mL/min
|
0 Participants
n=232 Participants • Note 1 subject randomized discontinued prior to treatment due to an adverse event
|
0 Participants
n=232 Participants • Note 1 subject randomized discontinued prior to treatment due to an adverse event
|
0 Participants
n=464 Participants • Note 1 subject randomized discontinued prior to treatment due to an adverse event
|
|
Screening Creatinine Clearance Group
> or = 20 to 30 mL/min
|
4 Participants
n=232 Participants • Note 1 subject randomized discontinued prior to treatment due to an adverse event
|
1 Participants
n=232 Participants • Note 1 subject randomized discontinued prior to treatment due to an adverse event
|
5 Participants
n=464 Participants • Note 1 subject randomized discontinued prior to treatment due to an adverse event
|
|
Screening Creatinine Clearance Group
>30 to 40 mL/min
|
12 Participants
n=232 Participants • Note 1 subject randomized discontinued prior to treatment due to an adverse event
|
7 Participants
n=232 Participants • Note 1 subject randomized discontinued prior to treatment due to an adverse event
|
19 Participants
n=464 Participants • Note 1 subject randomized discontinued prior to treatment due to an adverse event
|
|
Screening Creatinine Clearance Group
>40 to 50 mL/min
|
16 Participants
n=232 Participants • Note 1 subject randomized discontinued prior to treatment due to an adverse event
|
19 Participants
n=232 Participants • Note 1 subject randomized discontinued prior to treatment due to an adverse event
|
35 Participants
n=464 Participants • Note 1 subject randomized discontinued prior to treatment due to an adverse event
|
|
Screening Creatinine Clearance Group
> 50 mL/min
|
200 Participants
n=232 Participants • Note 1 subject randomized discontinued prior to treatment due to an adverse event
|
205 Participants
n=232 Participants • Note 1 subject randomized discontinued prior to treatment due to an adverse event
|
405 Participants
n=464 Participants • Note 1 subject randomized discontinued prior to treatment due to an adverse event
|
|
Age, Customized
< 65 years of age
|
159 Participants
n=233 Participants
|
155 Participants
n=232 Participants
|
314 Participants
n=465 Participants
|
|
Age, Customized
65 to 75 years of age
|
52 Participants
n=233 Participants
|
42 Participants
n=232 Participants
|
94 Participants
n=465 Participants
|
|
Age, Customized
> 75 years of age
|
22 Participants
n=233 Participants
|
35 Participants
n=232 Participants
|
57 Participants
n=465 Participants
|
|
Sex: Female, Male
Female
|
151 Participants
n=233 Participants
|
146 Participants
n=232 Participants
|
297 Participants
n=465 Participants
|
|
Sex: Female, Male
Male
|
82 Participants
n=233 Participants
|
86 Participants
n=232 Participants
|
168 Participants
n=465 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=233 Participants
|
0 Participants
n=232 Participants
|
0 Participants
n=465 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
233 Participants
n=233 Participants
|
232 Participants
n=232 Participants
|
465 Participants
n=465 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=233 Participants
|
0 Participants
n=232 Participants
|
0 Participants
n=465 Participants
|
PRIMARY outcome
Timeframe: TOC Visit (Day 19)Population: Microbiologic Modified Intent-to-Treat (m-MITT) population was used to assess overall success.
Clinical cure (resolution or significant improvement in signs and symptoms) and microbiologic eradication (baseline pathogen) in m-MITT population
Outcome measures
| Measure |
ZTI-01
n=184 Participants
6 g ZTI-01 (IV fosfomycin) intravenously administered every 8 hours (18g total daily dose for 7-14 calendar days)
ZTI-01: 6g ZTI-01 intravenous infusion TID q8 hours
|
Piperacillin Tazobactam
n=178 Participants
4.5 g piperacillin/tazobactam (4 g piperacillin/0.5 g tazobactam) intravenously administered every 8 hours (13.5g total daily dose for 7-14 calendar days)
Piperacillin-tazobactam: 4.5g piperacillin-tazobactam intravenous infusion TID q8 hours
|
|---|---|---|
|
Number of Patients With an Overall Success
|
119 Participants
|
97 Participants
|
SECONDARY outcome
Timeframe: TOC Visit (Day 19)Population: Microbiologic Modified Intent-to-Treat (m-MITT) population was used to assess clinical cure.
mMITT
Outcome measures
| Measure |
ZTI-01
n=184 Participants
6 g ZTI-01 (IV fosfomycin) intravenously administered every 8 hours (18g total daily dose for 7-14 calendar days)
ZTI-01: 6g ZTI-01 intravenous infusion TID q8 hours
|
Piperacillin Tazobactam
n=178 Participants
4.5 g piperacillin/tazobactam (4 g piperacillin/0.5 g tazobactam) intravenously administered every 8 hours (13.5g total daily dose for 7-14 calendar days)
Piperacillin-tazobactam: 4.5g piperacillin-tazobactam intravenous infusion TID q8 hours
|
|---|---|---|
|
Number of Patients With a Response of Clinical Cure in Various Protocol Populations
|
167 Participants
|
163 Participants
|
SECONDARY outcome
Timeframe: TOC Visit (Day 19)Population: Microbiologic Modified Intent-to-Treat (m-MITT) population was used to assess microbiologic eradication.
mMITT
Outcome measures
| Measure |
ZTI-01
n=184 Participants
6 g ZTI-01 (IV fosfomycin) intravenously administered every 8 hours (18g total daily dose for 7-14 calendar days)
ZTI-01: 6g ZTI-01 intravenous infusion TID q8 hours
|
Piperacillin Tazobactam
n=178 Participants
4.5 g piperacillin/tazobactam (4 g piperacillin/0.5 g tazobactam) intravenously administered every 8 hours (13.5g total daily dose for 7-14 calendar days)
Piperacillin-tazobactam: 4.5g piperacillin-tazobactam intravenous infusion TID q8 hours
|
|---|---|---|
|
Number of Patients With a Response of Microbiologic Eradication
|
121 Participants
|
100 Participants
|
Adverse Events
ZTI-01
Serious events: 5 serious events
Other events: 55 other events
Deaths: 0 deaths
Piperacillin Tazobactam
Serious events: 6 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ZTI-01
n=233 participants at risk
6 g ZTI-01 (IV fosfomycin) intravenously administered every 8 hours (18g total daily dose for 7-14 calendar days)
ZTI-01: 6g ZTI-01 intravenous infusion TID q8 hours
|
Piperacillin Tazobactam
n=231 participants at risk
4.5 g piperacillin/tazobactam (4 g piperacillin/0.5 g tazobactam) intravenously administered every 8 hours (13.5g total daily dose for 7-14 calendar days)
Piperacillin-tazobactam: 4.5g piperacillin-tazobactam intravenous infusion TID q8 hours
|
|---|---|---|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.43%
1/233
|
0.00%
0/231
|
|
Infections and infestations
Urinary Tract Infection
|
0.43%
1/233
|
0.43%
1/231
|
|
Infections and infestations
Acute Media Otitis
|
0.43%
1/233
|
0.00%
0/231
|
|
Infections and infestations
Prostatic Abscess
|
0.43%
1/233
|
0.00%
0/231
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic Gastric Cancer
|
0.43%
1/233
|
0.00%
0/231
|
|
Infections and infestations
Renal Abscess
|
0.00%
0/233
|
0.43%
1/231
|
|
Infections and infestations
Septic Embolus
|
0.00%
0/233
|
0.43%
1/231
|
|
Infections and infestations
Pyelonephritis Acute
|
0.00%
0/233
|
0.43%
1/231
|
|
Renal and urinary disorders
Renal Impairment
|
0.00%
0/233
|
0.43%
1/231
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/233
|
0.43%
1/231
|
Other adverse events
| Measure |
ZTI-01
n=233 participants at risk
6 g ZTI-01 (IV fosfomycin) intravenously administered every 8 hours (18g total daily dose for 7-14 calendar days)
ZTI-01: 6g ZTI-01 intravenous infusion TID q8 hours
|
Piperacillin Tazobactam
n=231 participants at risk
4.5 g piperacillin/tazobactam (4 g piperacillin/0.5 g tazobactam) intravenously administered every 8 hours (13.5g total daily dose for 7-14 calendar days)
Piperacillin-tazobactam: 4.5g piperacillin-tazobactam intravenous infusion TID q8 hours
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
4.3%
10/233
|
1.3%
3/231
|
|
Gastrointestinal disorders
Diarrhea
|
3.9%
9/233
|
4.8%
11/231
|
|
Gastrointestinal disorders
Vomiting
|
3.9%
9/233
|
0.43%
1/231
|
|
General disorders
Infusion site phlebitis
|
0.86%
2/233
|
2.6%
6/231
|
|
Investigations
Alanine aminotransferase increased
|
8.6%
20/233
|
2.6%
6/231
|
|
Investigations
Aspartate aminotransferase increased
|
7.3%
17/233
|
2.6%
6/231
|
|
Metabolism and nutrition disorders
Hypokalemia
|
6.0%
14/233
|
1.3%
3/231
|
|
Nervous system disorders
Headache
|
2.6%
6/233
|
2.2%
5/231
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60