Web Accessible Population Pharmacokinetics Service - Hemophilia: Sources of Variability (WAPPS-Hemo)

March 14, 2023 updated by: McMaster University

Exploring Sources of Variability in Individual Pharmacokinetics of Factor VIII and IX Concentrates in Hemophilia in the Web Accessible Population Pharmacokinetics Service - Hemophilia (WAPPS-Hemo) Database

Using anonymized patient data collected as part of the WAPPS-Hemo project to explore the sources of variability in individual pharmacokinetics (PK); use the sources of variability to improve the performance of the WAPPS-Hemo models through the addition of the predictors of PK variability as covariates.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

Innovation and expected results: As the classical PK approach typically requires 11 samples, which can be a burden to the patient, specific subgroups of individuals are often excluded from analysis-including children, elderly and critical care patients. As WAPPS-Hemo is the largest database of individual PK data, a large subgroup of pediatric patients and patients with inhibitors are available for investigation, allowing for analysis of variability in previously unavailable groups. Determining predictors of variability within patient outcome will allow us to improve the current models used to estimate individual PK, resulting in better individual care and use of resources.

Eligibility criteria: All valid data in the WAPPS-Hemo database will be used. All factor concentrates will be included. All available covariates will be analyzed.

Patients: Individuals with hemophilia A or B, any severity, who are registered on WAPPS-Hemo and for whom infusion and/or PK data are available. Both adult and pediatric patients will be included. Patients with history of inhibitors will be included as a separate subgroup.

Available covariates: age, sex, weight, height, dose and type of factor administered (as total and IU/kg), blood group, baseline factor level, positive history of inhibitors, hematocrit, hemoglobin, serum creatinine and laboratory methods used to measure factor VIII and factor IX.

Design: retrospective data analysis

Study database: The WAPPS-Hemo database will be used for the study. WAPPS-Hemo is a web accessible platform developed and run by the Health Information Research Unit (HiRU) at McMaster University. Data have been provided from participating hemophilia treatment centers worldwide to the scope of obtaining individual PK estimates. Data collected are completely anonymized, and re-use of the data for modelling and validation purposes was agreed upon by the inputting physicians, who committed to inform their patients about use of their data for system improvement.

Data extraction procedure: Data will be extracted from the WAPPS-Hemo database after transforming the centre name into a numeric code. The data extracted will include: patient age, sex, weight, height, dose and type of factor administered (as total and IU/kg), blood group, baseline factor level, positive history of inhibitors, hematocrit, hemoglobin, serum creatinine, laboratory methods used to measure factor VIII and factor IX, infused dose, post-infusion measurement of plasma factor activity level, estimated terminal half-life and time to 0.01, 0.02, and 0.05 IU/mL, with their credibility intervals, area under the curve (AUC), central volume, and clearance. Once extracted, the data will be stored in a secure server, located within the local network of the HiRU, protected by a proxy server and firewall.

Data cleaning: Once extracted, the data will be cleaned. Duplicate submissions will be removed, and all original data that has been duplicated from merged infusions will be deleted. Any data not valid for modelling, such as user input errors, insufficient data, or conditions that exclude use of patient data (such as use of inhibitors) will be removed and excluded from analysis. The dataset will be analyzed to search for outliers. Input errors missed at the source will be corrected where the incorrect measurement has been used (i.e. weight, height).

Data Analysis: Multivariate hierarchical analysis will be performed on various factors (age, sex, weight, height, dose and type of factor administered (as total and IU/kg), blood group, baseline factor level, positive history of inhibitors, hematocrit, hemoglobin, and serum creatinine, laboratory methods used to measure factor VIII and factor IX) to explore sources of variability in patient outcome. Significant predictors will be used as covariates in improvement of the model.

Study Type

Observational

Enrollment (Anticipated)

1000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8S4B2
        • McMaster University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Participates are individuals with hemophilia A or B, any severity, who have agreed to input of their data in the WAPPS-Hemo database, and who have sufficient infusion/PK data.

Description

Inclusion Criteria:

  • individuals with hemophilia A or B
  • infusion/PK data is available on the WAPPS-Hemo database
  • given informed consent to data input on the WAPPS-Hemo database

Exclusion Criteria:

- individuals currently undergoing immune tolerance induction

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Variability in individual PK
Patients with hemophilia A or B, of any severity, who are registered on the web-accessible population pharmacokinetics- hemophilia (WAPPS-Hemo) database, and for whom infusion and/or PK data is available.
Other: Variability in individual PK
Multivariate hierarchical analysis will be performed on various factors (age, sex, weight, height, dose and type of factor administered (as total and IU/kg), blood group, baseline factor level, positive history of inhibitors, hematocrit, hemoglobin, and serum creatinine, laboratory methods used to measure factor VIII and factor IX) to explore sources of variability in patient outcome.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sources of variability in individual pharmacokinetics for factor VII and IX concentrates
Time Frame: 2 years
Multivariate hierarchical analysis will be performed on various factors (age, sex, weight, height, dose and type of factor administered (as total and IU/kg), blood group, baseline factor level, positive history of inhibitors, hematocrit, hemoglobin, and serum creatinine, laboratory methods used to measure factor VIII and factor IX) to explore sources of variability in patient outcome. Significant predictors will be used as covariates to improve the performance of WAPPS-Hemo models.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

McMaster University

Investigators

  • Principal Investigator: Alfonso Iorio, McMaster University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 9, 2018

Primary Completion (Anticipated)

June 30, 2024

Study Completion (Anticipated)

June 30, 2024

Study Registration Dates

First Submitted

May 10, 2018

First Submitted That Met QC Criteria

May 10, 2018

First Posted (Actual)

May 23, 2018

Study Record Updates

Last Update Posted (Actual)

March 15, 2023

Last Update Submitted That Met QC Criteria

March 14, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 14-601-D

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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