MK-7625A Versus Meropenem in Pediatric Participants With... | NCT03230838

ID	Type	Description	Link
2016-004153-32	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Ceftolozane/Tazobactam	Experimental	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	Drug: Ceftolozane/Tazobactam
Meropenem	Active Comparator	Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days	Drug: Meropenem

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Ceftolozane/Tazobactam	Drug	12 to <18 years of age: Ceftolozane 1 g/dose; Tazobactam 0.5 g/dose via a 60-minute (±10 minutes) IV infusion every 8 hours for 7-14 days. <12 years of age: Ceftolozane 20 mg/kg with Tazobactam 10 mg/kg (not to exceed Ceftolozane 1 g and Tazobactam 0.5 g) via a 60-minute (±10 minutes) IV infusion every 8 hours for 7-14 days.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With ≥1 Adverse Events (AEs)	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.	Up to Day 88
Number of Participants Discontinuing Study Therapy Due to AE	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.	Up to Day 15

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With a Clinical Response of Cure at the Test of Cure Visit	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has a legally acceptable representative who provides documented informed consent / assent for the trial.
Ages from birth (defined as >32 weeks gestational age and ≥7 days postnatal) to <18 years of age.
Requires IV antibacterial therapy for the treatment of cUTI.
Have a pretreatment baseline urine culture specimen obtained within 48 hours before the start of administration of the first dose of study treatment and preferably prior to administration of any potentially therapeutic antibiotics.
Has pyuria.
Has clinical signs and/or symptoms of cUTI at the Screening Visit.
Is not of reproductive potential; but if of reproductive potential agrees to avoid becoming pregnant or impregnating a partner during screening, while receiving study treatment and for at least 30 days after the last dose of study treatment.
Female of reproductive potential is not pregnant, and not planning to become pregnant within 30 days of the last day of treatment administration; and is nonlactating.

Exclusion Criteria:

Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days prior to the first dose of study treatment in this current trial.
Has previously participated in any trial of ceftolozane or ceftolozane/tazobactam or has enrolled previously in the current trial and been discontinued.
Has a history of any moderate or severe hypersensitivity (e.g.anaphylaxis), allergic reaction, or other contraindication to any of the following: β-lactam antibiotics (e.g, penicillins, cephalosporins, and carbapenems), β-lactamase inhibitors (e.g. tazobactam, sulbactam, clavulanic acid, avibactam), or metronidazole.
Has a history of a cUTI within the past 1 year prior to randomization known to be caused by a pathogen resistant to either IV study treatment.
Has a concomitant infection at the time of randomization that requires nonstudy systemic antibacterial therapy in addition to IV study treatment or oral step -down therapy.
Has received potentially therapeutic antibacterial therapy for a duration more than 24 hours during the 48 hours preceding the first dose of study treatment.
Has any of the following: a) intractable UTI or pyelonephritis infection at baseline that the Investigator anticipates would require more than 14 days of study treatment; b) confirmed fungal urinary tract infection at time of randomization; c) permanent indwelling bladder catheter or instrumentation including nephrostomy; d) current urinary catheter that is not scheduled to be removed before the end of all study treatment; e) complete, permanent obstruction of the urinary tract; f) suspected or confirmed perinephric or intrarenal abscess; g) documented ileal loop reflux; h) suspected or confirmed prostatitis, urethritis, or epididymitis; i) trauma to pelvis/urinary tract.
Has moderate or severe impairment of renal function.
Has a seizure disorder or is anticipated to be treated with divalproex sodium or valproic acid during the course of study treatment.
Is receiving, or is expected to receive, any prohibited medications.
Has any rapidly progressing disease or immediately life-threatening illness, including acute hepatic failure, respiratory failure, or septic shock.
Has an immunocompromising condition.
Has a history of malignancy ≤5 years prior to signing informed consent.
Is planning to receive suppressive/prophylactic antibiotics with gram-negative activity after completion of study treatment.

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Children's Hospital - Los Angeles ( Site 2509)		Los Angeles	California	90027	United States
Children's Hospital of Orange County ( Site 2502)

PubMed Identifier	Type	Citation	Retractions
36689671	Result	Roilides E, Ashouri N, Bradley JS, Johnson MG, Lonchar J, Su FH, Huntington JA, Popejoy MW, Bensaci M, De Anda C, Rhee EG, Bruno CJ. Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonates and Children With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized Clinical Trial. Pediatr Infect Dis J. 2023 Apr 1;42(4):292-298. doi: 10.1097/INF.0000000000003832. Epub 2023 Jan 23.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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
FG001	Meropenem

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Sep 14, 2020

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With ≥1 Adverse Events (AEs)

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.

All randomized participants who received any amount of study treatment.

Posted

Count of Participants

Participants

Up to Day 88

ID	Title	Description
OG000	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
OG001	Meropenem	Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days

Units	Counts
Participants	OG000100 OG00133

Title

Denominators

Categories

Title	Measurements
	OG00059 OG00120

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Difference in Percentage (C/T minus Mero)					Percentage Difference	-1.6			2-Sided	95	-19.7	17.9			Ceftolozane/Tazobactam (C/T) minus Meropenem (Mero)		Other	The Miettinen & Nurminen method was used.

Primary

Number of Participants Discontinuing Study Therapy Due to AE

All randomized participants who received any amount of study treatment.

Posted

Count of Participants

Participants

Up to Day 15

ID	Title	Description
OG000	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
OG001	Meropenem	Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days

Units

Secondary

Percentage of Participants With a Clinical Response of Cure at the Test of Cure Visit

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.

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.

Posted

Number

95% Confidence Interval

Percentage of participants

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

ID	Title	Description
OG000	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
OG001	Meropenem	Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days

Units	Counts
Participants

Secondary

Percentage of Participants With a Clinical Response of Cure at the End of Treatment Visit

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.

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.

Posted

Number

95% Confidence Interval

Percentage of participants

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

ID	Title	Description
OG000	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
OG001	Meropenem	Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days

Units	Counts
Participants

Secondary

Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the Test of Cure Visit

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.

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.

Posted

Number

95% Confidence Interval

Percentage of participants

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

ID	Title	Description
OG000	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
OG001	Meropenem	Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days

Units	Counts
Participants

Secondary

Percentage of Participants With Microbiological Eradication of All Baseline Pathogens at the End of Treatment Visit

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.

Posted

Number

95% Confidence Interval

Percentage of participants

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

ID	Title	Description
OG000	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
OG001	Meropenem	Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pyrexia	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected100 at risk EG0011 events1 affected33 at risk
Pyelonephritis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected100 at risk EG0010 events0 affected33 at risk
Pyelonephritis acute	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected100 at risk EG0010 events0 affected33 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected100 at risk EG0010 events0 affected33 at risk
Hypertension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected100 at risk EG0011 events1 affected33 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Thrombocytosis	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0007 events7 affected100 at risk EG0013 events3 affected33 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0007 events7 affected100 at risk EG0013 events3 affected33 at risk
Pyrexia	General disorders	MedDRA 23.0	Systematic Assessment	EG0009 events6 affected100 at risk EG0010 events0 affected33 at risk
Rhinitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected100 at risk EG0012 events2 affected33 at risk
Urinary tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected100 at risk EG0013 events3 affected33 at risk
Vulvovaginitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected100 at risk EG0012 events2 affected33 at risk
Alanine aminotransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0004 events4 affected100 at risk EG0012 events2 affected33 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0004 events4 affected100 at risk EG0012 events2 affected33 at risk

ID	Term
D009395	Nephritis, Interstitial
D009393	Nephritis
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D011702	Pyelitis
D052801	Male Urogenital Diseases

ID	Term
D013845	Thienamycins
D015780	Carbapenems
D047090	beta-Lactams
D007769	Lactams
D000577	Amides
D009930	Organic Chemicals
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
BG000	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
BG001	Meropenem	Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ceftolozane/Tazobactam	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.	0	101	3	100	25	100
EG001	Meropenem	Meropenem 20 mg/kg (maximum 1 g/dose) administered IV every 8 hours for 7-14 days	0	33	2	33	10	33

ID	Term
C000594038	ceftolozane, tazobactam drug combination
D000077731	Meropenem