SepsisPhase 1NCT04147221
Imipenem-Relebactam Pharmacokinetics in Augmented Renal Clearance
A Phase 1 study testing Imipenem-relebactam in people with Sepsis, run by Hartford Hospital at 1 site in United States.
Trial summary
Critically ill patients with sepsis undergo several physiological alterations that can alter the distribution, metabolism, and elimination of drugs. Some patients with sepsis may realize enhanced cardiac output leading to increases in glomerular filtration that result in increasing drug clearance. Read more about this study
- Who is it for?
- Ages 18 to 54 years
- Conditions the study is for
- Sepsis
- What is being tested?
- Imipenem-relebactam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Feb 2020to 19 Sep 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 54 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- APACHE II score > 12 and ≤ 35;
- Creatinine clearance (CrCL) ≥150 mL/min (as calculated by the Cockcroft-Gault equation using ideal or adjusted body weight) within 24 hours of dosing;
- Documented infection or presumed infection as confirmed by the presence of at least one of the following criteria within the past 72 hours:
- Documented fever (oral, rectal, tympanic, or core temperature > 38.5° C)
- Hypothermia (oral, rectal, tympanic, or core temperature < 35.0° C)
- An elevated white blood cell (WBC) count ≥ 12,000 cells/mm3
Who cannot join
- If female, currently pregnant or breast feeding;
- History of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antibiotic (Note: mild rash or erythema to penicillin or cephalosporin antibiotics would not disqualify a patient if they have received a carbapenem without problem);
- History of chronic kidney disease, hemodialysis, or peritoneal dialysis; or history of acute renal replacement therapy (e.g., hemodialysis, hemofiltration, hemodiafiltration) or extracorporeal membrane oxygenation (ECMO) associated with current illness;
- Suspected rhabdomyolysis or creatine kinase > 10,000 U/L;
- Any serum creatinine (SCr) before dosing that is increased ≥ 0.3 mg/dL from the baseline SCr used qualifying for enrollment;
- Urinary output <20 ml/hour for at least 2 hours (oliguria) within 24 hours before enrollment;
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- Sustained (at least 1 hour) hypotension (systolic pressure < 90 mmHG or mean arterial pressure < 55 mmHg) refractory to vasopressors or intravenous fluid resuscitation for at least 24 hours before enrollment;
- Significant anemia defined as a hemoglobin < 8 g/dL at baseline;
- Use of probenecid, valproic acid, or imipenem within 3 days before study drug infusion;
- Acute liver injury, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times the upper limit of normal, or AST or ALT > 3 times the upper limit of normal with an associated total bilirubin > 2 times upper limit of normal;
- Any rapidly-progressing disease or immediately life-threatening illness (defined as imminent death within 48 hours in the opinion of the investigator);
- Any condition or circumstance that, in the opinion of the investigator, would compromise the safety of the patient or the quality of study data;
- Planned or prior participation in any other interventional drug study within 30 days.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label Pharmacokinetic Study of Imipenem-Relebactam in Critically Ill Patients With Augmented Renal Clearance
Critically ill patients with sepsis undergo several physiological alterations that can alter the distribution, metabolism, and elimination of drugs. Some patients with sepsis may realize enhanced cardiac output leading to increases in glomerular filtration that result in increasing drug clearance. This clinical state is referred as Augmented Renal Clearance (ARC). Importantly, many beta-lactam antibiotics can be adversely affected by ARC, and some of these agents required increasing dosage to compensate for enhanced clearance. Imipenem-relebactam is a new broad spectrum antibiotic. This study is designed to assess the pharmacokinetics of both components, imipenem and relebactam, in critically ill patients with ARC.
Read the detailed description
This is a single center, open-label study to determine imipenem-relebactam pharmacokinetics in critically ill patients with Augmented Renal Clearance (ARC). Twelve patients with suspected ARC will be enrolled to ensure complete pharmacokinetic data in at least eight patients with confirmed ARC. Confirmation of ARC will be established by eight hour urine creatine determination. Each participant will receive a single dose of imipenem-relebactam (500mg/250mg) followed by six blood samples over a 6 hour interval to determine concentrations. Non-compartmental and population pharmacokinetic analyses will be determined to assess the effects of ARC on imipenem and relebactam pharmacokinetic parameters.
- Conditions
- Sepsis
- Being tested
- Imipenem-relebactam
- Keywords
- beta-lactam, pharmacokinetics
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imipenem-relebactamDrug
After receipt of imipenem-relebactam, participants will have six blood samples collected over 6 hours for determination of imipenem and relebactam concentrations.
| Study group | Role | What they receive |
|---|---|---|
| Imipenem-Relebactam | Experimental | Participants will receive a single dose of intravenous imipenem-relebactam (500mg-250mg) as a 30 minute infusion. Receives: Drug: Imipenem-relebactam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Imipenem Clearance
The clearance in liters/hour of imipenem from the plasma of critically ill patients with augmented renal clearance
Measured: 6 hours [Timepoints taken at 0 hour (within 30 minutes prior to the start of infusion), 0.5 hours (end of infusion), 0.75, 1, 2, 4, and 6 hours after the start of the infusion]
Relebactam Clearance
The clearance in liters/hour of relebactam from the plasma of critically ill patients with augmented renal clearance
Measured: 6 hours [Timepoints taken at 0 hour (within 30 minutes prior to the start of infusion), 0.5 hours (end of infusion), 0.75, 1, 2, 4, and 6 hours after the start of the infusion]
Secondary outcomes (2)
Imipenem Area Under the Curve (AUC)
The AUC in milligram*hour/liter of imipenem calculated from concentrations collected between zero-6 hours and then extrapolated to infinity
Measured: 6 hours [Timepoints taken at 0 hour (within 30 minutes prior to the start of infusion), 0.5 hours (end of infusion), 0.75, 1, 2, 4, and 6 hours after the start of the infusion]
Relebactam Area Under the Curve (AUC)
The AUC in milligram*hour/liter of relebactam calculated from concentrations collected between zero-6 hours and then extrapolated to infinity
Measured: 6 hours [Timepoints taken at 0 hour (within 30 minutes prior to the start of infusion), 0.5 hours (end of infusion), 0.75, 1, 2, 4, and 6 hours after the start of the infusion]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2019
- Study start10 Feb 2020
- Primary completion10 Sep 2021
- Study completion19 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hartford Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Joseph Kuti, PharmD, Principal investigator, Hartford Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04147221
- Sponsor's protocol ID
- HHC-2019-0237
- Status last verified
- Aug 2024
- First submitted
- 29 Oct 2019
- Last updated
- 6 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Pharmacokinetic Study of Imipenem-Relebactam in Critically Ill Patients With Augmented Renal Clearance
- ClinicalTrials.gov ID
- NCT04147221
- Acronym / sponsor ID
- HHC-2019-0237
- Conditions
- Sepsis
- Keywords
- beta-lactam, pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Hartford HospitalUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 10 Feb 2020 (actual)
- Primary completion
- 10 Sep 2021 (actual)
- Study completion
- 19 Sep 2021 (actual)
- First posted
- 1 Nov 2019 (actual)
- Results
- Posted 6 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Critically ill patients with sepsis undergo several physiological alterations that can alter the distribution, metabolism, and elimination of drugs. Some patients with sepsis may realize enhanced cardiac output leading to increases in glomerular filtration that result in increasing drug clearance. This clinical state is referred as Augmented Renal Clearance (ARC). Importantly, many beta-lactam antibiotics can be adversely affected by ARC, and some of these agents required increasing dosage to compensate for enhanced clearance. Imipenem-relebactam is a new broad spectrum antibiotic. This study is designed to assess the pharmacokinetics of both components, imipenem and relebactam, in critically ill patients with ARC.
Detailed description
This is a single center, open-label study to determine imipenem-relebactam pharmacokinetics in critically ill patients with Augmented Renal Clearance (ARC). Twelve patients with suspected ARC will be enrolled to ensure complete pharmacokinetic data in at least eight patients with confirmed ARC. Confirmation of ARC will be established by eight hour urine creatine determination. Each participant will receive a single dose of imipenem-relebactam (500mg/250mg) followed by six blood samples over a 6 hour interval to determine concentrations. Non-compartmental and population pharmacokinetic analyses will be determined to assess the effects of ARC on imipenem and relebactam pharmacokinetic parameters.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Imipenem-Relebactam | Experimental | Drug: Imipenem-relebactamParticipants will receive a single dose of intravenous imipenem-relebactam (500mg-250mg) as a 30 minute infusion. |
Who may qualify
- Ages
- 18 to 54 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- APACHE II score > 12 and ≤ 35;
- Creatinine clearance (CrCL) ≥150 mL/min (as calculated by the Cockcroft-Gault equation using ideal or adjusted body weight) within 24 hours of dosing;
- Documented infection or presumed infection as confirmed by the presence of at least one of the following criteria within the past 72 hours:
Key exclusion criteria (13 listed)
- If female, currently pregnant or breast feeding;
- History of any moderate or severe hypersensitivity or allergic reaction to any β-lactam antibiotic (Note: mild rash or erythema to penicillin or cephalosporin antibiotics would not disqualify a patient if they have received a carbapenem without problem);
- History of chronic kidney disease, hemodialysis, or peritoneal dialysis; or history of acute renal replacement therapy (e.g., hemodialysis, hemofiltration, hemodiafiltration) or extracorporeal membrane oxygenation (ECMO) associated with current illness;
- Suspected rhabdomyolysis or creatine kinase > 10,000 U/L;
- Any serum creatinine (SCr) before dosing that is increased ≥ 0.3 mg/dL from the baseline SCr used qualifying for enrollment;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Imipenem-relebactamAfter receipt of imipenem-relebactam, participants will have six blood samples collected over 6 hours for determination of imipenem and relebactam concentrations. | Drug | Imipenem-Relebactam |
Primary outcome
Imipenem Clearance
Time frame: 6 hours [Timepoints taken at 0 hour (within 30 minutes prior to the start of infusion), 0.5 hours (end of infusion), 0.75, 1, 2, 4, and 6 hours after the start of the infusion]
The clearance in liters/hour of imipenem from the plasma of critically ill patients with augmented renal clearance
Relebactam Clearance
Time frame: 6 hours [Timepoints taken at 0 hour (within 30 minutes prior to the start of infusion), 0.5 hours (end of infusion), 0.75, 1, 2, 4, and 6 hours after the start of the infusion]
The clearance in liters/hour of relebactam from the plasma of critically ill patients with augmented renal clearance
2 secondary outcomes
Imipenem Area Under the Curve (AUC)
Time frame: 6 hours [Timepoints taken at 0 hour (within 30 minutes prior to the start of infusion), 0.5 hours (end of infusion), 0.75, 1, 2, 4, and 6 hours after the start of the infusion]
Relebactam Area Under the Curve (AUC)
Time frame: 6 hours [Timepoints taken at 0 hour (within 30 minutes prior to the start of infusion), 0.5 hours (end of infusion), 0.75, 1, 2, 4, and 6 hours after the start of the infusion]
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Kuti, PharmD principal investigator
Hartford Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Imipenem-relebactam in people with Sepsis, run by Hartford Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Imipenem Clearance (time frame: 6 hours [Timepoints taken at 0 hour (within 30 minutes prior to the start of infusion), 0.5 hours (end of infusion), 0.75, 1, 2, 4, and 6 hours after the start of the infusion]). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2024.