Trial Outcomes & Findings for MK-7625A Versus Meropenem in Pediatric Participants With Complicated Urinary Tract Infection (cUTI) (MK-7625A-034) (NCT NCT03230838)

Last Updated: 2023-05-06

Results Overview

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

134 participants

Primary outcome timeframe

Up to Day 88

Results posted on

2023-05-06

Participant Flow

Males and females from birth (\>32 weeks gestational age and ≥7 days postnatal), to \<18 years of age with complicated urinary tract infection (cUTI), including pyelonephritis, were enrolled in this study.

Participant milestones

Participant milestones
Measure	Ceftolozane/Tazobactam Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days	Meropenem Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days
Overall Study STARTED	101	33
Overall Study Treated	100	33
Overall Study COMPLETED	97	33
Overall Study NOT COMPLETED	4	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Ceftolozane/Tazobactam Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days	Meropenem Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days
Overall Study Withdrawal by Subject	3	0
Overall Study Temperature excursion	1	0

Baseline Characteristics

MK-7625A Versus Meropenem in Pediatric Participants With Complicated Urinary Tract Infection (cUTI) (MK-7625A-034)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ceftolozane/Tazobactam n=101 Participants Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days	Meropenem n=33 Participants Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days	Total n=134 Participants Total of all reporting groups
Age, Continuous	5.3 Years STANDARD_DEVIATION 5.3 • n=5 Participants	5.5 Years STANDARD_DEVIATION 5.7 • n=7 Participants	5.4 Years STANDARD_DEVIATION 5.4 • n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	20 Participants n=7 Participants	85 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	13 Participants n=7 Participants	49 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	5 Participants n=7 Participants	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	81 Participants n=5 Participants	27 Participants n=7 Participants	108 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	1 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	100 Participants n=5 Participants	33 Participants n=7 Participants	133 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Day 88

Population: All randomized participants who received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam n=100 Participants Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days	Meropenem n=33 Participants Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days
Number of Participants With ≥1 Adverse Events (AEs)	59 Participants	20 Participants

PRIMARY outcome

Timeframe: Up to Day 15

Population: All randomized participants who received any amount of study treatment.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam n=100 Participants Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days	Meropenem n=33 Participants Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days
Number of Participants Discontinuing Study Therapy Due to AE	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Test of Cure Visit (up to 35 days)

Population: All randomized participants who received any amount of study treatment and have at least 1 acceptable causative uropathogen identified from a study-qualifying baseline urine culture.

Clinical response of cure is complete resolution or marked improvement in signs and symptoms of the complicated urinary tract infection (cUTI) or return to pre-infection signs and symptoms, such that no further antibiotic therapy (IV or oral) is required for the treatment of the cUTI. The 95% confidence intervals (CIs) of each treatment are unstratified Wilson CIs.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam n=71 Participants Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days	Meropenem n=24 Participants Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days
Percentage of Participants With a Clinical Response of Cure at the Test of Cure Visit	88.7 Percentage of participants Interval 79.31 to 94.18	95.8 Percentage of participants Interval 79.76 to 99.26

SECONDARY outcome

Timeframe: Up to 48 hours after last oral dose (up to 19 days)

Population: All randomized participants who received any amount of study treatment and have at least 1 acceptable causative uropathogen identified from a study-qualifying baseline urine culture.

Clinical response of cure is complete resolution or marked improvement in signs and symptoms of the cUTI or return to pre-infection signs and symptoms, such that no further antibiotic therapy (IV or oral) is required for the treatment of the cUTI. The 95% CIs of each treatment are unstratified Wilson CIs.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam n=71 Participants Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days	Meropenem n=24 Participants Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days
Percentage of Participants With a Clinical Response of Cure at the End of Treatment Visit	94.4 Percentage of participants Interval 86.39 to 97.79	100.0 Percentage of participants Interval 86.2 to 100.0

SECONDARY outcome

Timeframe: Up to Test of Cure Visit (up to 35 days)

Population: All randomized participants who received any amount of study treatment and have at least 1 acceptable causative uropathogen identified from a study-qualifying baseline urine culture.

Microbiological eradication of all baseline pathogens is defined as a postbaseline urine culture shows all uropathogens found at baseline at ≥10\^5 colony-forming units (CFU)/mL are reduced to \<10\^4 CFU/mL. The 95% CIs of each treatment are unstratified Wilson CIs.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam n=71 Participants Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days	Meropenem n=24 Participants Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days
Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the Test of Cure Visit	84.5 Percentage of participants Interval 74.35 to 91.12	87.5 Percentage of participants Interval 69.0 to 95.66

SECONDARY outcome

Timeframe: Up to 48 hours after last oral dose (up to 19 days)

Population: All randomized participants who received any amount of study treatment and have at least 1 acceptable causative uropathogen identified from a study-qualifying baseline urine culture.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam n=71 Participants Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered intravenously (IV) every 8 hours for 7-14 days	Meropenem n=24 Participants Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days
Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the End of Treatment Visit	93.0 Percentage of participants Interval 84.55 to 96.95	95.8 Percentage of participants Interval 79.76 to 99.26

Adverse Events

Ceftolozane/Tazobactam

Serious events: 3 serious events

Other events: 25 other events

Deaths: 0 deaths

Meropenem

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ceftolozane/Tazobactam n=100 participants at risk Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered IV every 8 hours for 7-14 days.	Meropenem n=33 participants at risk Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days
General disorders Pyrexia	0.00% 0/100 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.	3.0% 1/33 • Number of events 1 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.
Infections and infestations Pyelonephritis	1.0% 1/100 • Number of events 1 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.	0.00% 0/33 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.
Infections and infestations Pyelonephritis acute	1.0% 1/100 • Number of events 1 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.	0.00% 0/33 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.
Infections and infestations Upper respiratory tract infection	1.0% 1/100 • Number of events 1 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.	0.00% 0/33 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.
Vascular disorders Hypertension	0.00% 0/100 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.	3.0% 1/33 • Number of events 1 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.

Other adverse events

Other adverse events
Measure	Ceftolozane/Tazobactam n=100 participants at risk Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose) administered IV every 8 hours for 7-14 days.	Meropenem n=33 participants at risk Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days
Blood and lymphatic system disorders Thrombocytosis	7.0% 7/100 • Number of events 7 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.	9.1% 3/33 • Number of events 3 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.
Gastrointestinal disorders Diarrhoea	7.0% 7/100 • Number of events 7 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.	9.1% 3/33 • Number of events 3 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.
General disorders Pyrexia	6.0% 6/100 • Number of events 9 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.	0.00% 0/33 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.
Infections and infestations Rhinitis	2.0% 2/100 • Number of events 2 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.	6.1% 2/33 • Number of events 2 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.
Infections and infestations Urinary tract infection	1.0% 1/100 • Number of events 1 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.	9.1% 3/33 • Number of events 3 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.
Infections and infestations Vulvovaginitis	0.00% 0/100 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.	6.1% 2/33 • Number of events 2 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.
Investigations Alanine aminotransferase increased	4.0% 4/100 • Number of events 4 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.	6.1% 2/33 • Number of events 2 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.
Investigations Aspartate aminotransferase increased	4.0% 4/100 • Number of events 4 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.	6.1% 2/33 • Number of events 2 • Adverse Events (AEs): From treatment (Day 1) up to 88 days. All-cause mortality: From randomization (Day 1) up to 88 days. For all-cause mortality the population analyzed was all randomized participants. For AEs the population analyzed was all randomized participants who received any amount of study treatment.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results.
Publication restrictions are in place

Restriction type: OTHER