Vancomycin treatment in critically ill adults using model-informed precision dosing tool – prospective low-intervention clinical trial. (ProVanc)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Tartu University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

1 Mar 2024 → 1 Feb 2026

Decision date (initial)

2024-01-12

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic

To prospectively evaluate the performance of the model selection and model-informed precision dosing tool developed by our study group in achieving desirable intravenous vancomycin exposure target over 70% of the treatment time.

Secondary objectives 3

1. To assess vancomycin treatment AUC24 based target attainment while doses are optimised using the model selection and model-informed precision dosing tool developed by our study group.
2. To assess safety of the vancomycin model selection and model-informed precision dosing tool developed by our study group.
3. To determine whether effective AUC24 can be achieved with concentrations in lower Ctrough based TDM range 10-15 mg/kg.

Conditions and MedDRA coding

Serious infections where according to the treating physician's decision treatment with intravenous vancomycin is needed.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Age ≥18 years
2. Admitted to the tertiary intensive care unit in Tartu University Hospital
3. Patient has indication (assessed by treating doctor) to start intravenous vancomycin treatment

Exclusion criteria 6

1. Patient has been previously enrolled into this study during ongoing hospital record
2. Patient has previously received vancomycin within last 7 days
3. Intravenous treatment with vancomycin has begun more than 24h before enrolment to study
4. The treating physician considers the patient not suitable for the study
5. There is no intention for vancomycin therapeutic drug monitoring
6. Continues intravenous vancomycin administration is used

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of patients that stay in the vancomycin therapeutic target range (AUC24 400-600 µg/ml x h) 70% of time when dose is optimised using the model selection and model-informed precision dosing tool developed by our study group

Secondary endpoints 15

1. Median proportion of time during vancomycin treatment spent within the vancomycin therapeutic target range AUC24 400-600 µg/mL x hr
2. Proportion of patients who achieve the treatment goal of AUC24 400-600 µg/mL x hr during the first 24h
3. Proportion of patients who achieve the treatment goal of AUC24 400-600 µg/mL x hr between 24-48h after the initiation of treatment with vancomycin
4. Proportion of patients with average AUC24 in target range
5. Mortality at the discharge from 3rd level intensive care unit
6. Length of hospitalisation and stay in the third level ICU
7. Length of vancomycin treatment
8. Attainment of clinical cure, defined as survival and completion of the antibiotic therapy course without addition of or switch to another antibiotic therapy and no start of a new antibiotic assessed at the study end visit
9. Clinical outcome by the end of study defined as following: dead, alive in ICU, referred to home, referred to another hospital ward
10. The cumulative vancomycin dose
11. Corresponding vancomycin AUC24 and Ctrough during the treatment period
12. Occurrence and worsening of acute kidney injury (according to the KDIGO AKI criteria) during vancomycin treatment
13. Percentage of measured vancomycin Ctrough values exceeding 20 mg/L
14. Proportion of time spent above the recommended AUC24 >600 µg/mL x hr
15. The proportion of Ctrough values under, over or in the target ranges (<10 mg/L, 10-20 mg/L, 10-15 mg/L, 15-20 mg/L, >20 mg/L) compared to corresponding AUC24

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Tartu University Hospital

Sponsor organisation

Tartu University Hospital

Address

L. Puusepa Tn 1a

City

Tartu Linn

Postcode

50406

Country

Estonia

Scientific contact point

Organisation

Tartu University Hospital

Contact name

Hanna Kadri Laas

Public contact point

Organisation

Tartu University Hospital

Contact name

Hanna Kadri Laas

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications