Trial Outcomes & Findings for Imipenem/Cilastatin/Relebactam PK in ECMO (NCT NCT04493151)
NCT ID: NCT04493151
Last Updated: 2024-08-07
Results Overview
The clearance in liters/hour of imipenem from the plasma of critically ill patients receiving ECMO.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
8 participants
Primary outcome timeframe
6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).
Results posted on
2024-08-07
Participant Flow
Participant milestones
| Measure |
Imipenem-Cilastatin-Relebactam
Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.
Imipenem, Cilastatin and Relebactam: After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.
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|---|---|
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Overall Study
STARTED
|
8
|
|
Overall Study
COMPLETED
|
7
|
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Overall Study
NOT COMPLETED
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1
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Imipenem/Cilastatin/Relebactam PK in ECMO
Baseline characteristics by cohort
| Measure |
Imipenem-Cilastatin-Relebactam
n=7 Participants
Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.
Imipenem, Cilastatin and Relebactam: After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.
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|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
|
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Age, Categorical
Between 18 and 65 years
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7 Participants
n=5 Participants
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Age, Categorical
>=65 years
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0 Participants
n=5 Participants
|
|
Age, Continuous
|
50 Years
STANDARD_DEVIATION 16 • n=5 Participants
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Sex: Female, Male
Female
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2 Participants
n=5 Participants
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Sex: Female, Male
Male
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5 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Hispanic or Latino
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1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
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4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
|
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Race (NIH/OMB)
Black or African American
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2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
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Region of Enrollment
United States
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7 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).The clearance in liters/hour of imipenem from the plasma of critically ill patients receiving ECMO.
Outcome measures
| Measure |
Imipenem-Cilastatin-Relebactam
n=7 Participants
Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.
Imipenem, Cilastatin and Relebactam: After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.
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|---|---|
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Imipenem Clearance
|
15.21 Liters per hour
Standard Deviation 6.52
|
PRIMARY outcome
Timeframe: 6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).The clearance in liters/hour of relebactam from the plasma of critically ill patients receiving ECMO.
Outcome measures
| Measure |
Imipenem-Cilastatin-Relebactam
n=7 Participants
Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.
Imipenem, Cilastatin and Relebactam: After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.
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|---|---|
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Relebactam Clearance
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6.95 Liters per hour
Standard Deviation 1.34
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SECONDARY outcome
Timeframe: 6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).The AUC in milligram\*hour/liter of imipenem calculated from concentrations collected between zero and 6 hours at steady-state
Outcome measures
| Measure |
Imipenem-Cilastatin-Relebactam
n=7 Participants
Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.
Imipenem, Cilastatin and Relebactam: After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.
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|---|---|
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Imipenem Area Under the Curve (AUC)
|
36.9 mg*h/L
Standard Deviation 13.3
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SECONDARY outcome
Timeframe: 6 hours (samples collected before the first imipenem/cilastatin/relebactam dose (i.e., blank), and at 0.5 and 6 hours following the first dose, and then at 0, 0.5, 0.75, 1, 2, 4, 5, and 6 hours after the start of the final dose).The AUC in milligram\*hour/liter of relebactam calculated from concentrations collected between zero and 6 hours at steady-state
Outcome measures
| Measure |
Imipenem-Cilastatin-Relebactam
n=7 Participants
Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.
Imipenem, Cilastatin and Relebactam: After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.
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|---|---|
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Relebactam Area Under the Curve (AUC)
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45.3 mg*h/L
Standard Deviation 33.2
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Adverse Events
Imipenem-Cilastatin-Relebactam
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Imipenem-Cilastatin-Relebactam
n=8 participants at risk
Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.
Imipenem, Cilastatin and Relebactam: After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.
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|---|---|
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Hepatobiliary disorders
Alkaline Phosphate Increase
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12.5%
1/8 • Number of events 1 • Adverse events were collected over a 48 hour window, from the first imipenem-relebactam dose (0 hour) to the end of blood sampling (6 hours), plus an 24 hour observation window after the last sample was collected, culminating with physical exam. Note: 8 subjects were enrolled and received imipenem-relebactam. Although only 7 subjects were included in results analysis due to inability to obtain blood samples in 1 subject, all 8 subjects are included in the adverse event reporting.
Adverse event - any pathologic or unintended change in the structure (signs), function (symptoms), or chemistry (laboratory values) of the body associated with the use of the study drug, whether or not considered drug related: MILD - present, but easily tolerated MODERATE - discomfort that interferes with usual activities SEVERE - incapacitating, inability to work or do usual activities
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Gastrointestinal disorders
C. difficile Diarrhea
|
12.5%
1/8 • Number of events 1 • Adverse events were collected over a 48 hour window, from the first imipenem-relebactam dose (0 hour) to the end of blood sampling (6 hours), plus an 24 hour observation window after the last sample was collected, culminating with physical exam. Note: 8 subjects were enrolled and received imipenem-relebactam. Although only 7 subjects were included in results analysis due to inability to obtain blood samples in 1 subject, all 8 subjects are included in the adverse event reporting.
Adverse event - any pathologic or unintended change in the structure (signs), function (symptoms), or chemistry (laboratory values) of the body associated with the use of the study drug, whether or not considered drug related: MILD - present, but easily tolerated MODERATE - discomfort that interferes with usual activities SEVERE - incapacitating, inability to work or do usual activities
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Infections and infestations
Increasing Leukocytosis
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25.0%
2/8 • Adverse events were collected over a 48 hour window, from the first imipenem-relebactam dose (0 hour) to the end of blood sampling (6 hours), plus an 24 hour observation window after the last sample was collected, culminating with physical exam. Note: 8 subjects were enrolled and received imipenem-relebactam. Although only 7 subjects were included in results analysis due to inability to obtain blood samples in 1 subject, all 8 subjects are included in the adverse event reporting.
Adverse event - any pathologic or unintended change in the structure (signs), function (symptoms), or chemistry (laboratory values) of the body associated with the use of the study drug, whether or not considered drug related: MILD - present, but easily tolerated MODERATE - discomfort that interferes with usual activities SEVERE - incapacitating, inability to work or do usual activities
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Hepatobiliary disorders
Aspartate Aminotransferase Increase
|
12.5%
1/8 • Number of events 1 • Adverse events were collected over a 48 hour window, from the first imipenem-relebactam dose (0 hour) to the end of blood sampling (6 hours), plus an 24 hour observation window after the last sample was collected, culminating with physical exam. Note: 8 subjects were enrolled and received imipenem-relebactam. Although only 7 subjects were included in results analysis due to inability to obtain blood samples in 1 subject, all 8 subjects are included in the adverse event reporting.
Adverse event - any pathologic or unintended change in the structure (signs), function (symptoms), or chemistry (laboratory values) of the body associated with the use of the study drug, whether or not considered drug related: MILD - present, but easily tolerated MODERATE - discomfort that interferes with usual activities SEVERE - incapacitating, inability to work or do usual activities
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Additional Information
Dr. Joseph L. Kuti, PharmD, FIDP, FCCP
Center for Anti-Infective Research and Development, Hartford Hospital
Phone: (860) 972-3612
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place