Ignite Creation Date:
2025-12-24 @ 6:44 PM
Ignite Modification Date:
2026-03-14 @ 5:31 AM
Study NCT ID:
NCT05618457
Status:
RECRUITING
Last Update Posted:
2024-03-01
First Post:
2022-10-30
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Adjustment of Aminoglycoside Dosing Based on Peak Serum Concentration and Bacterial Minimal Inhibitory Concentration
Sponsor:
Hadassah Medical Organization
Organization:
Study Overview
Official Title:
Adjustment of Aminoglycoside Dosing Based on Peak Serum Concentration and Bacterial Minimal Inhibitory Concentration
Status:
RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 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.
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.
1. If Cmax/MIC=8-12 - no intervention (aminoglycoside dose unchanged).
2. If Cmax/MIC\>12 - decreasing AG dose accordingly, based on clinical calculators, to achieve target Cmax/MIC\~10;
3. 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.
4. If AG dose has been adjusted, ascertaining PK/PD target attainment (repeat timely peak level determination following dose adjustment).
5. 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)
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.
1. If Cmax/MIC=8-12 - no intervention (aminoglycoside dose unchanged).
2. If Cmax/MIC\>12 - decreasing AG dose accordingly, based on clinical calculators, to achieve target Cmax/MIC\~10;
3. 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.
4. If AG dose has been adjusted, ascertaining PK/PD target attainment (repeat timely peak level determination following dose adjustment).
5. 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 Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: