Aminoglycoside Dosing Based on PK/PD CharacteristicsNCT05618457
Adjustment of Aminoglycoside Dosing Based on Peak Serum Concentration and Bacterial Minimal Inhibitory Concentration
A study testing Aminoglycoside dose adjustment in people with Aminoglycoside Dosing Based on PK/PD Characteristics, run by Hadassah Medical Organization at 1 site in Israel.
Trial summary
Aminoglycoside (AG) antibiotics have been in clinical use since the 1960s for treating various infections. The main safety concern related to AG use is nephrotoxicity. Based on validated pharmacokinetic-pharmacodynamic (PK-PD) principles shown to predict efficacy, AG dosing has shifted over the past 2 decades from… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aminoglycoside Dosing Based on PK/PD Characteristics
- What is being tested?
- Aminoglycoside dose adjustment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 151 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Dec 2021to 31 Dec 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
None listed.
Who cannot join
- Age<18yr
- Neurosurgical infections, pneumonia, endocarditis or endovascular infections
- eGFR<40ml/min
- Empirical aminoglycoside treatment
- Non Gram-negative pathogen
- No MIC available for the pathogen
- Expected remaining treatment duration of less than 4 days
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Hadassah Hebrew University Medical Center
Jerusalem, 12000
Maya Korem, MD, +972508573173, MayaK@hadassah.org.il
EHud Horwitz, PhD, +972502799755, ehud.horwitz@mail.huji.ac.il
About this study
Aminoglycoside (AG) antibiotics have been in clinical use since the 1960s for treating various infections. The main safety concern related to AG use is nephrotoxicity. Based on validated pharmacokinetic-pharmacodynamic (PK-PD) principles shown to predict efficacy, AG dosing has shifted over the past 2 decades from multiple daily dosing to extended-interval dosing, with concomitant reduction in nephrotoxicity. Currently, AG daily dose is calculated according to the patients' adjusted body weight, assuming a common minimal inhibitory concentration (MIC) value.
We hypothesize that once pathogen identity and actual MIC become available, AG daily doses may be further adjusted, using the same PK-PD indices.
In order to investigate this hypothesis, we are conducting a prospective clinical study in which AG doses will be adjusted based on patient- and pathogen-specific factors, while assessing efficacy and safety.
Read the detailed description
Intervention for all eligible patients:
calculation of Cmax/MIC based on MIC determination and timely peak level determination performed 30 minutes after the first or second AG dose following pathogen identity and MIC availability (as Individual timely monitoring is essential for individual dose adjustment, this will require one additional blood sample to routine clinical practice). If a peak-level monitoring is not available, Cmax will be assessed using commonly used pharmacokinetic prediction tools (equations/calculators.
- If Cmax/MIC=8-12 - no intervention (aminoglycoside dose unchanged).
- If Cmax/MIC>12 - decreasing AG dose accordingly, based on clinical calculators, to achieve target Cmax/MIC~10;
- If Cmax/MIC<8 - increasing AG dose accordingly, based on clinical calculators, to achieve target Cmax/MIC~10; If the calculated dose is larger than acceptable AG dosing, an infectious diseases physician will be consulted for need for alternative therapy.
- If AG dose has been adjusted, ascertaining PK/PD target attainment (repeat timely peak level determination following dose adjustment).
- Monitoring clinical and microbiological course and outcomes:
5.1 Clinical efficacy microbiological and clinical cure, in-hospital mortality 5.2 Safety - renal function during therapy, at end of therapy and at discharge or at day 7 after end of therapy, whichever is earlier. Any deterioration in renal function compared with baseline will be categorized according to the RIFLE criteria.
5.3 Aminoglycoside dosing data (proportion end extent of dose adjustments performed)
- Being tested
- Aminoglycoside dose adjustment
- Keywords
- Aminoglycosides, Minimal Inhibitory Concentration (MIC), Gram negative, PK/PD, Peak concentration (Cmax)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aminoglycoside dose adjustmentDrug
Eligible patients may have the aminoglycoside dose adjusted based on pathogen MIC, to attain the PK/PD target of Cam/MIC~10 (8-12)
| Study group | Role | What they receive |
|---|---|---|
| Aminoglycoside dose adjustment | Other | Eligible patients will be assessed for attainment of PK/PD target under standard dosing, dose adjustment to attain target will be proposed where appropriate Receives: Drug: Aminoglycoside dose adjustment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy outcome
proportion of patients where treatment failure was suspected and attributed to AG dose reduction
Measured: up to 1 week after end of therapy
Renal outcome
Proportion of patients fulfilling RIFLE criteria (any category) baseline
Measured: up to 1 week after end of therapy
Renal outcome
Mean serum creatinine change at end of therapy vs. baseline
Measured: up to 1 week after end of therapy
Aminoglycoside dosing outcomes:
Proportion of patients where AG dose was adjusted based on PK-PD parameters
Measured: up to 1 week after end of therapy
Aminoglycoside dosing outcomes:
Mean change in AG dose following adjustment
Measured: up to 1 week after end of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2022
- Study start1 Dec 2021
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aminoglycoside Dosing Based on PK/PD CharacteristicsStudies of the same condition, open and under way.
- More trials run by Hadassah Medical OrganizationThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 151 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Maya Korem, MD, Principal investigator, Director, Antimicrobial Stewardship Program
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05618457
- Sponsor's protocol ID
- 0557-21-HMO
- Status last verified
- Feb 2024
- First submitted
- 30 Oct 2022
- Last updated
- 1 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: YES
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjustment of Aminoglycoside Dosing Based on Peak Serum Concentration and Bacterial Minimal Inhibitory Concentration
- ClinicalTrials.gov ID
- NCT05618457
- Acronym / sponsor ID
- 0557-21-HMO
- Keywords
- Aminoglycosides, Minimal Inhibitory Concentration (MIC), Gram negative, PK/PD, Peak concentration (Cmax)
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 151 participants (estimated)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 16 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Aminoglycoside (AG) antibiotics have been in clinical use since the 1960s for treating various infections. The main safety concern related to AG use is nephrotoxicity. Based on validated pharmacokinetic-pharmacodynamic (PK-PD) principles shown to predict efficacy, AG dosing has shifted over the past 2 decades from multiple daily dosing to extended-interval dosing, with concomitant reduction in nephrotoxicity. Currently, AG daily dose is calculated according to the patients' adjusted body weight, assuming a common minimal inhibitory concentration (MIC) value.
We hypothesize that once pathogen identity and actual MIC become available, AG daily doses may be further adjusted, using the same PK-PD indices.
In order to investigate this hypothesis, we are conducting a prospective clinical study in which AG doses will be adjusted based on patient- and pathogen-specific factors, while assessing efficacy and safety.
Detailed description
Intervention for all eligible patients:
calculation of Cmax/MIC based on MIC determination and timely peak level determination performed 30 minutes after the first or second AG dose following pathogen identity and MIC availability (as Individual timely monitoring is essential for individual dose adjustment, this will require one additional blood sample to routine clinical practice). If a peak-level monitoring is not available, Cmax will be assessed using commonly used pharmacokinetic prediction tools (equations/calculators.
- If Cmax/MIC=8-12 - no intervention (aminoglycoside dose unchanged).
- If Cmax/MIC>12 - decreasing AG dose accordingly, based on clinical calculators, to achieve target Cmax/MIC~10;
- If Cmax/MIC<8 - increasing AG dose accordingly, based on clinical calculators, to achieve target Cmax/MIC~10; If the calculated dose is larger than acceptable AG dosing, an infectious diseases physician will be consulted for need for alternative therapy.
- If AG dose has been adjusted, ascertaining PK/PD target attainment (repeat timely peak level determination following dose adjustment).
- Monitoring clinical and microbiological course and outcomes:
5.1 Clinical efficacy microbiological and clinical cure, in-hospital mortality 5.2 Safety - renal function during therapy, at end of therapy and at discharge or at day 7 after end of therapy, whichever is earlier. Any deterioration in renal function compared with baseline will be categorized according to the RIFLE criteria.
5.3 Aminoglycoside dosing data (proportion end extent of dose adjustments performed)
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Aminoglycoside dose adjustment | Other | Drug: Aminoglycoside dose adjustmentEligible patients will be assessed for attainment of PK/PD target under standard dosing, dose adjustment to attain target will be proposed where appropriate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (7 listed)
- Age<18yr
- Neurosurgical infections, pneumonia, endocarditis or endovascular infections
- eGFR<40ml/min
- Empirical aminoglycoside treatment
- Non Gram-negative pathogen
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 |
|---|---|---|
| Aminoglycoside dose adjustmentEligible patients may have the aminoglycoside dose adjusted based on pathogen MIC, to attain the PK/PD target of Cam/MIC~10 (8-12) | Drug | Aminoglycoside dose adjustment |
Primary outcome
Efficacy outcome
Time frame: up to 1 week after end of therapy
proportion of patients where treatment failure was suspected and attributed to AG dose reduction
Renal outcome
Time frame: up to 1 week after end of therapy
Proportion of patients fulfilling RIFLE criteria (any category) baseline
Renal outcome
Time frame: up to 1 week after end of therapy
Mean serum creatinine change at end of therapy vs. baseline
Aminoglycoside dosing outcomes:
Time frame: up to 1 week after end of therapy
Proportion of patients where AG dose was adjusted based on PK-PD parameters
Aminoglycoside dosing outcomes:
Time frame: up to 1 week after end of therapy
Mean change in AG dose following adjustment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2024.
- Individual participant dataSharing planned: Undecided. YES
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.
Maya Korem, MD principal investigator
Director, Antimicrobial Stewardship Program
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Aminoglycoside dose adjustment in people with Aminoglycoside Dosing Based on PK/PD Characteristics, run by Hadassah Medical Organization at 1 site in Israel.
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 0 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 1 Mar 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 Israel. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ehud Horwitz, PhD (+972502799755, ehud.horwitz@mail.huji.ac.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy outcome (time frame: up to 1 week after end of therapy). The study lists 5 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 1 Mar 2024.