SepsisPhase 1NCT04493151

Imipenem/Cilastatin/Relebactam PK in ECMO

A Phase 1 study testing Imipenem, Cilastatin and Relebactam in people with Sepsis, run by Joseph L. Kuti, PharmD at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Sepsis
What is being tested?: Imipenem, Cilastatin and Relebactam
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 8 participants
Where: 1 siteUnited States
Study dates: 1 Jan 2021to 30 Jun 2023
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age 18 years or older;
On support with Veno-venous- or Veno-arterial-ECMO;
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 agent (a history of mild rash to a β-lactam followed by uneventful re-exposure is not a contraindication);
Severe renal dysfunction defined as a creatinine clearance < 15 mL/min (calculated by the Cockcroft-Gault equation using actual body weight) or requirement for continuous renal replacement therapy or hemodialysis;
Hemoglobin less than 8 mg/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;

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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.

United States1 site

Hartford Hospital
Hartford, Connecticut, 06102

Other trials in United States

About this study

Official title: Pharmacokinetics of Imipenem/Cilastatin/Relebactam in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation (ECMO)

Extracorporeal membrane oxygenation (ECMO) is a from of cardiopulmonary life-support for critically ill patients where blood is extracted from the vascular system and circulated by a mechanical pump while it is oxygenated and re-infused into the patient's circulation. It is well known that critically ill patients may experience alterations in antibiotic pharmacokinetics, and as a result, dosing modifications are generally required. There is a need to understand how ECMO circuits affect the pharmacokinetics and disposition of drugs. This study is designed to assess the pharmacokinetics of the new broad-spectrum antibiotic, imipenem-cilastatin-relebactam, in critically ill patients receiving ECMO.

Read the detailed description

This is a single center, open-label study to determine imipenem-cilastatin-relebactam pharmacokinetics in critically ill patients receiving ECMO. Eight patients with suspected suspected sepsis and who are receiving ECMO will be enrolled. Each participant will receive four to six doses of imipenem-cilastatin-relebactam according to current approved prescribing information, followed by ten blood samples to determine concentrations. Non-compartmental and population pharmacokinetic analyses will be determined to assess the effects of ECMO on imipenem and relebactam pharmacokinetic parameters.

Conditions: Sepsis
Being tested: Imipenem, Cilastatin and 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, Cilastatin and RelebactamDrug
Also called Recarbrio
After receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.

Study groups in NCT04493151
Study group	Role	What they receive
Imipenem-Cilastatin-Relebactam	Experimental	Participants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance. Receives: Drug: Imipenem, Cilastatin and 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 receiving ECMO.
Measured: 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).
Relebactam Clearance
The clearance in liters/hour of relebactam from the plasma of critically ill patients receiving ECMO.
Measured: 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).

Secondary outcomes (2)

Imipenem Area Under the Curve (AUC)
The AUC in milligram*hour/liter of imipenem calculated from concentrations collected between zero and 6 hours at steady-state
Measured: 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).
Relebactam Area Under the Curve (AUC)
The AUC in milligram*hour/liter of relebactam calculated from concentrations collected between zero and 6 hours at steady-state
Measured: 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).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jan 202130 Jun 2023

First posted30 Jul 2020
Study start1 Jan 2021
Primary completion31 May 2023
Study completion30 Jun 2023

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: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04493151
Sponsor's protocol ID: 59752
Status last verified: Aug 2024
First submitted: 27 Jul 2020
Last updated: 7 Aug 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Sepsis trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pharmacokinetics of Imipenem/Cilastatin/Relebactam in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation (ECMO)
ClinicalTrials.gov ID: NCT04493151
Acronym / sponsor ID: 59752
Conditions: Sepsis
Keywords: beta-lactam, pharmacokinetics
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 8 participants (actual)
Lead sponsor: Joseph L. Kuti, PharmDUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC
Study start: 1 Jan 2021 (actual)
Primary completion: 31 May 2023 (actual)
Study completion: 30 Jun 2023 (actual)
First posted: 30 Jul 2020 (actual)
Results: Posted 7 Aug 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Imipenem-Cilastatin-Relebactam	Experimental	Drug: Imipenem, Cilastatin and RelebactamParticipants will receive a four to six doses of intravenous imipenem-cilastatin-relebactam as per current prescribing information based on estimated creatinine clearance.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Age 18 years or older;
On support with Veno-venous- or Veno-arterial-ECMO;
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 (9 listed)

If female, currently pregnant or breast feeding;
History of any moderate or severe hypersensitivity or allergic reaction to any β-lactam agent (a history of mild rash to a β-lactam followed by uneventful re-exposure is not a contraindication);
Severe renal dysfunction defined as a creatinine clearance < 15 mL/min (calculated by the Cockcroft-Gault equation using actual body weight) or requirement for continuous renal replacement therapy or hemodialysis;
Hemoglobin less than 8 mg/dL at baseline;
Use of probenecid, valproic acid, or imipenem within 3 days before study drug infusion;

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, Cilastatin and RelebactamAlso: RecarbrioAfter receipt of imipenem-cilastatin-relebactam, ten blood samples will be collected to determine the pharmacokinetics of imipenem and relebactam.	Drug	Imipenem-Cilastatin-Relebactam

Primary outcome

Imipenem Clearance
Time frame: 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.
Relebactam Clearance
Time frame: 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.

2 secondary outcomes

Imipenem Area Under the Curve (AUC)
Time frame: 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).
Relebactam Area Under the Curve (AUC)
Time frame: 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 and safety

Results posted to the registry on 7 Aug 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Imipenem-Cilastatin-Relebactam	8	7

Primary outcome: Imipenem Clearance

Time frame: 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).. Mean (Standard Deviation). Unit: Liters per hour

Measure	Imipenem-Cilastatin-Relebactam n = 7
Value	15.21 (6.52)

Primary outcome: Relebactam Clearance

Measure	Imipenem-Cilastatin-Relebactam n = 7
Value	6.95 (1.34)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Imipenem-Cilastatin-Relebactam	0 of 8 (0%)	3 of 8 (37.5%)	0 of 8

Limitations and caveats (from the sponsor): A study limitation is the protocol defined exclusion of patients on concomitant continuous renal replacement therapy (CRRT), which is common in patients receiving ECMO (extracorporeal membrane oxygenation). Dosing modifications may be necessary in patients receiving both CRRT and ECMO.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Sepsis

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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 L 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, Cilastatin and Relebactam in people with Sepsis, run by Joseph L. Kuti, PharmD 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 9 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 7 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 7 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 (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 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?

On the ClinicalTrials.gov record for NCT04493151.

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 7 Aug 2024.