NCT04510805

Effectiveness of NextDose for Warfarin Dose Individualization

Single-blind, Randomized Comparison of Warfarin Management Guided by NextDose Versus Management Based on Clinician Experience.

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 240 (estimated)
• Sponsor: The First Affiliated Hospital of Soochow University · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Objectives: To understand whether the implementation of warfarin dose management using NextDose (nextdose.org) at The First Affiliated Hospital of Soochow University (Suzhou, China) improves the quality of anticoagulation therapy. Endpoint Primary 1\. Percentage of time within the acceptable INR range estimated using linear interpolation during the 28 days after initiation of warfarin. Secondary 2.1 Percentage of Time Measures 2.2 Time to Stable Dose 2.3 Safety Outcomes 2.4 Acceptability of NextDose Recommendations Exploratory 3.1 Percentage of Time Measures 3.2 Time to Stable Dose 3.3 Safety Outcomes 3.4 Acceptability of NextDose Recommendations 3.5 Model Evaluation 3.6 INR Variability Population: 240 participants of any sex between the age of 18 and 80 years. Patients requiring treatment with warfarin following cardiac surgery.

Detailed description

Objectives: To understand whether the implementation of warfarin dose management using NextDose (nextdose.org) at The First Affiliated Hospital of Soochow University (Suzhou, China) improves the quality of anticoagulation therapy. Endpoint Primary 1. Percentage of time within the acceptable INR range estimated using linear interpolation during the 28 days after initiation of warfarin. Secondary 2.1 Percentage of Time Measures 1. Percentage of time within the acceptable INR Range estimated using linear interpolation during the 90 days after initiation of warfarin. 2. Percentage of time spent above and below the acceptable INR range at day 28, and 90 after initiation of warfarin estimated by linear interpolation. 2.2 Time to Stable Dose a. Number of days to achievement of stable dose (defined as 3 consecutive INR measurements within acceptable range for the same mean daily dose). 2.3 Safety Outcomes a. Number of participants who experience at least one of the following safety events: major bleeding within 30 days, INR of 4 or greater within 30 days, death within 30 days, and symptomatic or asymptomatic VTE confirmed by objective testing within 60 days of surgery. 2.4 Acceptability of NextDose Recommendations 1. Percentage of prescribed doses within 0.625 mg of the NextDose proposed dose. 2. Mean difference between the prescribed dose and the NextDose proposed dose. Exploratory 3.1 Percentage of Time Measures a. The percentage of time spent within, above and below the acceptable INR range estimated by numerical integration with the Bayesian parameter estimates of the PKPD model at day 28 and at day 90 after initiation of warfarin. 3.2 Time to Stable Dose a) Days to first INR measurement within the acceptable range. b) Days to second consecutive INR measurement within the acceptable range. c) Number of dose adjustments to achievement of stable dose (3 consecutive INR measurements within acceptable range for the same mean daily dose). d) Total number of dose adjustments at day 90. e) Total number of INR measurements at day 90. 3.3 Safety Outcomes a) Incidence of minor and major bleeding events. b) Incidence of thromboembolic events. c) 30 day all-cause mortality. d) 90 day all-cause mortality. e) 90 day cardiovascular mortality. f) Number of warfarin doses withheld due to high INR (as determined by the treating clinician). 3.4 Acceptability of NextDose Recommendations a) Percentage of prescribed doses within 20% of the NextDose proposed dose. 3.5 Model Evaluation a) Predictive performance of the model for patients with steady-state warfarin doses below 2 or above 7 mg/day. 3.6 INR Variability a) INR variability as described by Lind et al. (the standard deviation of transformed INR values). Population: 240 participants of any sex between the age of 18 and 80 years. Patients requiring treatment with warfarin following cardiac surgery.

Conditions

• Thrombosis Embolism

Interventions

Type	Name	Description
DEVICE	NextDose (nextdose.org)	NextDose guided warfarin management taking into consideration covariates (sex, age, weight, height CYP2C9 (rs1057910) and VKORC1 (rs9923231), the dosing and INR history of each patient to predict an individualized dose in accordance with the theory-based warfarin model and target concentration intervention principles. Initial recommended warfarin dose, up to the first INR, will be the maintenance dose predicted from group values, subsequently the NextDose predicted maintenance dose will be recommended. The treating clinician will also be provided with the NextDose report to inform the choice of the prescribed dose.

Timeline

• Start date: 2020-08-01
• Primary completion: 2021-09-01
• Completion: 2021-12-01
• First posted: 2020-08-12
• Last updated: 2020-08-19