Trial Outcomes & Findings for MK-7625A Plus Metronidazole Versus Meropenem in Pediatric Participants With Complicated Intra-Abdominal Infection (cIAI) (MK-7625A-035) (NCT NCT03217136)

Last Updated: 2023-05-06

Results Overview

An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

94 participants

Primary outcome timeframe

Up to approximately 75 days

Results posted on

2023-05-06

Participant Flow

Paediatric participants were enrolled from 27 sites in 11 countries.

Participant milestones

Participant milestones
Measure	Ceftolozane/Tazobactam + Metronidazole Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose), plus metronidazole 10 mg/kg (maximum 1.5 g/day) administered intravenously (IV) every 8 to 12 hours for 5 to 14 days.	Meropenem Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for metronidazole administered IV every 8 hours for 5 to 14 days.
Overall Study STARTED	71	23
Overall Study Treated	70	21
Overall Study COMPLETED	67	20
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Ceftolozane/Tazobactam + Metronidazole Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose), plus metronidazole 10 mg/kg (maximum 1.5 g/day) administered intravenously (IV) every 8 to 12 hours for 5 to 14 days.	Meropenem Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for metronidazole administered IV every 8 hours for 5 to 14 days.
Overall Study Lost to Follow-up	2	1
Overall Study Site Randomized Participant in Error	0	1
Overall Study Did Not Meet Criteria after Randomization	0	1
Overall Study Dispensing Error	1	0
Overall Study Withdrawal by Parent/Guardian	1	0

Baseline Characteristics

MK-7625A Plus Metronidazole Versus Meropenem in Pediatric Participants With Complicated Intra-Abdominal Infection (cIAI) (MK-7625A-035)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ceftolozane/Tazobactam + Metronidazole n=71 Participants Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose), plus metronidazole 10 mg/kg (maximum 1.5 g/day) administered intravenously (IV) every 8 to 12 hours for 5 to 14 days.	Meropenem n=23 Participants Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for metronidazole administered IV every 8 hours for 5 to 14 days.	Total n=94 Participants Total of all reporting groups
Age, Continuous	8.7 Years STANDARD_DEVIATION 4.4 • n=5 Participants	8.6 Years STANDARD_DEVIATION 3.6 • n=7 Participants	8.7 Years STANDARD_DEVIATION 4.2 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	15 Participants n=7 Participants	38 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	8 Participants n=7 Participants	56 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants	7 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	50 Participants n=5 Participants	16 Participants n=7 Participants	66 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	0 Participants n=7 Participants	3 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	3 Participants n=5 Participants	2 Participants n=7 Participants	5 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	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	61 Participants n=5 Participants	20 Participants n=7 Participants	81 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 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 approximately 75 days

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

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam + Metronidazole n=70 Participants Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose), plus metronidazole 10 mg/kg (maximum 1.5 g/day) administered intravenously (IV) every 8 to 12 hours for 5 to 14 days.	Meropenem n=21 Participants Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for metronidazole administered IV every 8 hours for 5 to 14 days.
Number of Participants Experiencing ≥1 Adverse Events (AEs)	56 Participants	13 Participants

PRIMARY outcome

Timeframe: Up to approximately 18 days

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

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam + Metronidazole n=70 Participants Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose), plus metronidazole 10 mg/kg (maximum 1.5 g/day) administered intravenously (IV) every 8 to 12 hours for 5 to 14 days.	Meropenem n=21 Participants Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for metronidazole administered IV every 8 hours for 5 to 14 days.
Number of Participants Who Discontinued Study Therapy Due to AE(s)	2 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to approximately 27 days

Population: All randomized participants who received any amount of study treatment. Participants were included in the IV study treatment group to which they were randomized, irrespective of what treatment they actually received.

The percentage of participants who had a clinical outcome of "cure" at the time of the EOT visit is presented. The "cure" clinical outcome was defined as complete resolution or marked improvement in signs and symptoms of the complicated intra-abdominal infection (cIAI) or return to pre-infection signs and symptoms such that no further antibiotic therapy (intravenous or oral) or surgical or drainage procedure is required for treatment of the cIAI. Participants who were missing clinical response data were considered treatment failures.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam + Metronidazole n=70 Participants Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose), plus metronidazole 10 mg/kg (maximum 1.5 g/day) administered intravenously (IV) every 8 to 12 hours for 5 to 14 days.	Meropenem n=21 Participants Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for metronidazole administered IV every 8 hours for 5 to 14 days.
Percentage of Participants With a Clinical Response of "Cure" at the End of Treatment (EOT) Visit	80.0 Percentage of participants Interval 69.18 to 87.7	95.2 Percentage of participants Interval 77.33 to 99.15

SECONDARY outcome

Timeframe: Up to approximately 39 days

The percentage of participants who had a clinical outcome of "cure" at the time of the TOC visit is presented. The "cure" clinical outcome was defined as complete resolution or marked improvement in signs and symptoms of the complicated intra-abdominal infection (cIAI) or return to pre-infection signs and symptoms such that no further antibiotic therapy (intravenous or oral) or surgical or drainage procedure is required for treatment of the cIAI. Participants who were missing clinical response data were considered treatment failures.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam + Metronidazole n=70 Participants Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose), plus metronidazole 10 mg/kg (maximum 1.5 g/day) administered intravenously (IV) every 8 to 12 hours for 5 to 14 days.	Meropenem n=21 Participants Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for metronidazole administered IV every 8 hours for 5 to 14 days.
Percentage of Participants With a Clinical Response of "Cure" at the Test of Cure (TOC) Visit	80.0 Percentage of participants Interval 69.18 to 87.7	100.0 Percentage of participants Interval 84.54 to 100.0

SECONDARY outcome

Timeframe: Up to approximately 27 days

Population: All randomized participants who received any amount of study treatment and had at least 1 pathogen identified from the baseline intra-abdominal culture, regardless of susceptibility to study treatment. Participants were included in the IV study treatment group to which they were randomized, irrespective of what treatment they actually received.

The percentage of participants who achieved either eradication or presumed eradication of each baseline infecting pathogen by the time of the EOT visit is presented. Eradication was defined as absence of the baseline pathogen(s) in a postbaseline specimen appropriately obtained from the original site of infection. Presumed eradication was defined as absence of material to culture in a participant who is assessed as having partial improvement, or clinical cure. In the event of multiple baseline pathogens, the least favorable microbiological response from all possible baseline pathogens was used.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam + Metronidazole n=63 Participants Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose), plus metronidazole 10 mg/kg (maximum 1.5 g/day) administered intravenously (IV) every 8 to 12 hours for 5 to 14 days.	Meropenem n=19 Participants Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for metronidazole administered IV every 8 hours for 5 to 14 days.
Percentage of Participants With Microbiological Eradication at the EOT Visit	84.1 Percentage of participants Interval 73.19 to 91.14	94.7 Percentage of participants Interval 75.36 to 99.06

SECONDARY outcome

Timeframe: Up to approximately 39 days

The percentage of participants who achieved either eradication or presumed eradication of each baseline infecting pathogen by the time of the TOC visit is presented. Eradication was defined as absence of the baseline pathogen(s) in a postbaseline specimen appropriately obtained from the original site of infection. Presumed eradication was defined as absence of material to culture in a participant who is assessed as having partial improvement, or clinical cure. In the event of multiple baseline pathogens, the least favorable microbiological response from all possible baseline pathogens was used.

Outcome measures

Outcome measures
Measure	Ceftolozane/Tazobactam + Metronidazole n=63 Participants Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose), plus metronidazole 10 mg/kg (maximum 1.5 g/day) administered intravenously (IV) every 8 to 12 hours for 5 to 14 days.	Meropenem n=19 Participants Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for metronidazole administered IV every 8 hours for 5 to 14 days.
Percentage of Participants With Microbiological Eradication at the TOC Visit	84.1 Percentage of participants Interval 73.19 to 91.14	100 Percentage of participants Interval 83.18 to 100.0

Adverse Events

Ceftolozane/Tazobactam + Metronidazole

Serious events: 8 serious events

Other events: 46 other events

Deaths: 0 deaths

Meropenem

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ceftolozane/Tazobactam + Metronidazole n=70 participants at risk Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose), plus metronidazole 10 mg/kg (maximum 1.5 g/day) administered intravenously (IV) every 8 to 12 hours for 5 to 14 days.	Meropenem n=21 participants at risk Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for metronidazole administered IV every 8 hours for 5 to 14 days.
Gastrointestinal disorders Constipation	1.4% 1/70 • Number of events 1 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	0.00% 0/21 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Gastrointestinal disorders Faecaloma	1.4% 1/70 • Number of events 1 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	0.00% 0/21 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Gastrointestinal disorders Intestinal obstruction	1.4% 1/70 • Number of events 1 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	0.00% 0/21 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Gastrointestinal disorders Intra-abdominal fluid collection	1.4% 1/70 • Number of events 1 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	0.00% 0/21 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Infections and infestations Abdominal sepsis	1.4% 1/70 • Number of events 1 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	0.00% 0/21 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Infections and infestations Arthritis bacterial	1.4% 1/70 • Number of events 1 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	0.00% 0/21 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Infections and infestations Lower respiratory tract infection	1.4% 1/70 • Number of events 1 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	0.00% 0/21 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Infections and infestations Pneumonia	2.9% 2/70 • Number of events 2 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	0.00% 0/21 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Investigations White blood cell count increased	1.4% 1/70 • Number of events 1 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	0.00% 0/21 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.

Other adverse events

Other adverse events
Measure	Ceftolozane/Tazobactam + Metronidazole n=70 participants at risk Ceftolozane 20 mg/kg and tazobactam 10 mg/kg (maximum 1 g and 0.5 g/dose), plus metronidazole 10 mg/kg (maximum 1.5 g/day) administered intravenously (IV) every 8 to 12 hours for 5 to 14 days.	Meropenem n=21 participants at risk Meropenem 20 mg/kg (maximum 1 g/dose) plus placebo for metronidazole administered IV every 8 hours for 5 to 14 days.
Blood and lymphatic system disorders Anaemia	5.7% 4/70 • Number of events 4 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	0.00% 0/21 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Blood and lymphatic system disorders Thrombocytosis	8.6% 6/70 • Number of events 6 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	4.8% 1/21 • Number of events 1 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Cardiac disorders Tachycardia	7.1% 5/70 • Number of events 5 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	4.8% 1/21 • Number of events 1 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Gastrointestinal disorders Abdominal pain	10.0% 7/70 • Number of events 8 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	0.00% 0/21 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Gastrointestinal disorders Diarrhoea	18.6% 13/70 • Number of events 14 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	23.8% 5/21 • Number of events 5 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Gastrointestinal disorders Vomiting	10.0% 7/70 • Number of events 8 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	4.8% 1/21 • Number of events 1 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
General disorders Pyrexia	12.9% 9/70 • Number of events 10 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	14.3% 3/21 • Number of events 7 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Infections and infestations Nasopharyngitis	4.3% 3/70 • Number of events 3 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	14.3% 3/21 • Number of events 4 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Injury, poisoning and procedural complications Incision site pain	10.0% 7/70 • Number of events 7 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	4.8% 1/21 • Number of events 1 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Investigations Alanine aminotransferase increased	5.7% 4/70 • Number of events 4 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	4.8% 1/21 • Number of events 1 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Investigations Aspartate aminotransferase increased	7.1% 5/70 • Number of events 5 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	4.8% 1/21 • Number of events 1 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Investigations Platelet count increased	7.1% 5/70 • Number of events 5 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	9.5% 2/21 • Number of events 2 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.
Vascular disorders Hypertension	5.7% 4/70 • Number of events 4 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for all randomized participants who received any amount of study treatment.	0.00% 0/21 • Up to approximately 75 days Deaths are counted in the population of all randomized participants. Serious adverse events and non-serious adverse events are reported for 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