A Dried Blood Spot Sampling Method for Vancomycin and Creatinine Monitoring for OPAT (ADVANCEDOPAT)

A Dried Blood Spot Sampling Method for Vancomycin and Creatinine Monitoring: Effectiveness Demonstrated in Outpatient Parenteral Antibiotic Therapy Service

The Outpatient Parenteral Antibiotic Therapy (OPAT) service consists of providing antimicrobial therapy through parenteral infusion without hospitalization. This service is provided to stable patients otherwise ready for hospital discharge. Generally, the clinical monitoring for this patient population is minimal. However, clinical monitoring of vancomycin, an antibiotic widely used during OPAT, can be intensive primarily due to therapeutic drug monitoring. To ensure optimal treatment and minimize nephrotoxicity and microbial resistance, TDM and monitoring of serum creatinine levels are crucial during vancomycin therapy. TDM of vancomycin with OPAT presents a challenge for patients who must frequently travel to blood sampling facilities or the hospital for measurements. An alternative sampling method for TDM is the dried blood spot (DBS) method, which involves collecting a small drop of capillary blood from a finger prick onto filter paper. By implementing the DBS sampling method, the amount of outpatient visits regarding vancomycin treatment in OPAT can be reduced. Furthermore, the addition of measuring a biochemical parameter, such as renal function with serum creatinine, could lead to even less outpatient visits during OPAT. To date, studies investigating the effectiveness of DBS sampling of vancomycin and creatinine in terms of reducing outpatient visits have not yet been conducted in the OPAT population.

Study Overview

• Status: Recruiting
• Conditions: Infection, Bacterial
• Intervention / Treatment: Diagnostic test: Venipuncture; Diagnostic test: Finger Prick

Detailed Description

The use of vancomycin in OPAT services is widespread, however a drawback of its use is the need for laboratory monitoring of the vancomycin concentration which requires patients to travel to a blood sampling facility or the hospital for blood sampling. At most hospitals at least one or two blood samples per week are obtained for vancomycin drug monitoring from a patient in OPAT service receiving vancomycin. Conventional blood sampling involves an invasive procedure of drawing blood from a vene through a venipuncture, this is performed by a qualified health care worker at a blood drawing facility (often performed by a nurse in the hospital). Besides the burden for the patient to travel to a blood sampling facility the costs also have to be taken into account, contributing to a higher cost for OPAT services.

The hospital pharmacy laboratory of Erasmus University Medical Center has developed and clinically validated a dried blood spot (DBS) assay for measuring vancomycin and creatinine (ADVANCED study). The use of dried blood spot collection to quantify drug concentrations is an innovative technique that requires only a simple finger prick instead of an invasive venipuncture. Consequently, this is less painful and stressful for the patient than conventional blood sampling. DBS can be performed by taking a low-volume finger prick samples (10 to 20 μl) on filter paper. Finger samples can be taken and stored with a desiccant, without the need for processing and freezing of plasma. A small-diameter disc, or chad, can be subsequently punched out from the filter paper, and the drug can be eluted into a liquid matrix prior to a liquid chromatography-mass spectrometry (LC-MS) assay. The main benefit of DBS sampling is that it allows for the ease of self-sampling at home. DBS offers several other practical advantages over conventional plasma sampling. These advantages include lower sample volume requirements, simplified collection techniques, and less restrictive transport and storage conditions.

DBS sampling eliminates the need to travel to a sampling facility as no healthcare professionals are involved in the sampling process. To date, studies investigating the effectiveness of DBS sampling in terms of reducing outpatient visits have not been conducted in the OPAT population. OPAT is provided for patients who are stable and healthy enough to leave the hospital and clinical monitoring of these patient population is minimal. However, clinical monitoring of vancomycin therapy during OPAT is intensive due to TDM of vancomycin. Most protocols oblige at least once weekly TDM of vancomycin, which contributes to outpatient visits. By implementing DBS sampling the investigators hypothesize that the number of outpatient visits regarding vancomycin therapy in OPAT services can be reduced. Furthermore, this effectiveness may increase when a biochemical parameter such as renal function parameter (i.e. creatinine) are measured along with drug concentrations (leading to even less outpatient visits); the benefit of this has not been investigated yet.

• Study Type: Interventional
• Enrollment (Estimated): 84
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Birgit Koch, PharmD; Phone Number: 0107033202; Email: b.koch@erasmusmc.nl
• Study Contact Backup: Name: Moska Hassanzai, PharmD; Phone Number: 0107033202; Email: m.hassanzai@erasmusmc.nl

Study Locations

• Netherlands
  • Rotterdam, Netherlands
    • Recruiting
    • Erasmus MC
    • Contact: Birgit Koch, PharmD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18 and over
• Able to understand written information and able to give informed consent
• Hospitalized
• Treated with intravenous vancomycin and to be discharged with vancomycin OPAT service with minimal 1 planned outpatient vancomycin TDM order
• Able and willing to perform finger pricks for dried blood spot sampling, or able and willing to undergo finger pricks performed by family members or other caregivers
• Able and willing to fill in questionnaires

Exclusion Criteria:

• Former participation in this trial
• Cognitive dysfunction or other dysfunctionalities which makes the patient unable to draw blood by a finger prick or fill out questionnaires
• Unable to sample an adequate DBS after training in the hospital (this is also applicable for family members or other caregivers who are failing to perform adequate DBS sampling for the patient)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Group (venipuncture); Conventional blood sampling via venipuncture method by a skilled drawing facility	Diagnostic test: Venipuncture; Blood sample obtained trough venipuncture
Experimental: Intervention Group (DBS); Blood sampling via dried blood spotting (DBS) method at patient's home	Diagnostic test: Finger Prick; Blood sample obtained via drop of capillary blood by finger prick onto filter paper; Other Names: Dried Blood Spot Sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the number of outpatient visits in the control group versus the intervention group at day 28	Number of outpatient visits	28 days after discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Outcomes regarding outpatient visit	To compare the number of outpatient visits with the sole purpose of vancomycin TDM in the control group versus intervention group (phlebotomy visits); To compare the number of outpatient visits with the sole purpose of laboratory sampling (with and without TDM) in the control group versus intervention group; To compare the number of outpatient visits regarding vancomycin therapy without laboratory sampling in the control group versus intervention group; To compare the number of outpatient visits regarding vancomycin therapy including laboratory sampling (with and without TDM) in the control group versus intervention group; To compare the number of vancomycin therapy related telephone consultations in the control group versus intervention group	28 days after discharge
Sampling outcomes	- To compare the number of correct blood sampling in the control group versus intervention group	28 days after discharge
Satisfaction with blood sampling based on the theoretical framework of acceptability questionnaire (TFA)	- To investigate if dried blood spot sampling of vancomycin leads to a higher patient satisfaction score (questionnaire) compared with conventional sampling in OPAT service. A higher score means a higher patient satisfaction (maximum score is 7)	28 days after discharge
Cost outcomes	To compare patient costs in the control group versus intervention group; To compare costs related to loss of productivity in the control group versus intervention group; To compare health care costs in the control group versus intervention group; To compare societal costs (total of all costs) in the control group versus intervention group	28 days after discharge
Clinical outcomes	- To compare clinical outcomes in the control group versus intervention group	28 days after discharge
TDM outcomes	To compare the relative number of vancomycin measurements in the control group versus intervention group	28 days after discharge
Logistical outcomes	To compare the time of vancomycin blood sample arrival at the lab after sampling in the control group versus intervention group	28 days after discharge

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Investigators: Principal Investigator: Birgit Koch, PharmD, Erasmus MC University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: October 30, 2023
• First Submitted That Met QC Criteria: February 26, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: vancomycin; creatinine; dried blood spot; microsampling
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Bacterial Infections
• Other Study ID Numbers: NL83813.078.23

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No