Assessing the Clinical Benefits of a Pharmacogenetics-Guided Dosing Regiment for Calculating Warfarin Maintenance Dose

NCT00700895 | Unknown Phase 3 DMC

• 1 other identifier: PG01/11/06
• Study Type: interventional
• Target: 320
• Locations: 2 countries
• Sites: 2

Brief Summary

Interethnic differences in warfarin dose requirements in the Asian population have been well described. Our previous studies showed that warfarin maintenance doses in our multi-ethnic population were closely related to patient demographics and genetic polymorphisms in cytochrome(CYP)P4502C9 and vitamin K epoxide reductase complex subunit 1(VKORC1). A retrospective regression model combining these predictors accounts for 57.8% of the variability in warfarin dose.

Conditions

Indications for Warfarin Therapy

Outcome Measures

Primary Outcomes (1)

• No. of dosage titrations required to achieve targeted INR at 3 months of initializing warfarin.

  1\. Number of dosage titrations/adjustments required to achieve targeted International Normalized Ratio (INR) at 3 months of initializing warfarin. The number of titrations refers to the number of times warfarin dosage was adjusted when INR was out of target range (\>1.9 and ≤ 3.1) or in response to an adverse event or therapeutic failure. This endpoint will be compiled every 4 weeks, up to 3 months after the initialization of warfarin therapy

  3 months

Secondary Outcomes (1)

• pharmacokinetics of warfarin R- and S-enantiomers

  3 months

Study Arms (2)

Pharmacogenetics-guided dosing group

EXPERIMENTAL

For patients randomized to the pharmacogenetics-guided dosing group, this 10mls of blood will be immediately sent for genotyping studies. Genotyping results will be available for pharmacogenetics-guided dosing within 3 working days, (ranging 3 to 5 days). During this period, if patients need to be initiated on anticoagulation, a low molecular weight heparin, Fraxiparine, will be given. Fraxiparine will be overlapped with warfarin for 2 to 3 days until target INR is achieved. Elective cases should have the pharmacogenetics-based warfarin dose available at the time of warfarin therapy.

Drug: Warfarin Sodium

Traditional dosing group

EXPERIMENTAL

For patients randomized to the traditional dosing regime, the blood will be stored and genotyped retrospectively at the end of the study. Overlapping of warfarin with Fraxiparine or heparin till target INR is achieved is allowed for this group as per normal clinical practice. All warfarin dosage adjustments based on INR results will be according to the current protocol used by the NUH Anticoagulant Clinic.

Drug: Warfarin Sodium

Interventions

Warfarin Sodium DRUG

All predicted warfarin dose will be administered by rounding down to the nearest 0.5 mg. Warfarin (Marevan®) is available as 1mg (brown), 3 mg (blue) and 5 mg (pink) oral tablets from GlaxoSmithKline Pte. Ltd.

Also known as: Warfarin (Marevan®)

Pharmacogenetics-guided dosing group; Traditional dosing group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age
• New indication for warfarin therapy
• No previous history of liver disease; transaminases must be less than 3 times upper limit of normal and bilirubin within normal range
• No previous history of malabsorption syndrome or chronic diarrheal conditions
• Written, informed consent

You may not qualify if:

• Uncontrolled hypertension
• Peptic ulcer disease
• Any other medical conditions as deemed unfit for warfarin therapy based on clinical judgement of primary physician

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (2)

University of Malaya Medical Centre

Kuala Lumpur, 50603, Malaysia

RECRUITING

National University Hospital

Singapore, Singapore

RECRUITING

Related Publications (2)

• Wong HJ, Teo YN, Teo YH, Syn NL, Wong AL, Teoh HL, Seet RCS, Lee SC, Goh BC, Sia CH. Subgroup analysis of genotype guided vs traditional warfarin dosing in Asian patients from an open label randomized trial. Sci Rep. 2026 Jan 2;16(1):3670. doi: 10.1038/s41598-025-33831-9.

  PMID: 41484425 DERIVED

• Syn NL, Wong AL, Lee SC, Teoh HL, Yip JWL, Seet RC, Yeo WT, Kristanto W, Bee PC, Poon LM, Marban P, Wu TS, Winther MD, Brunham LR, Soong R, Tai BC, Goh BC. Genotype-guided versus traditional clinical dosing of warfarin in patients of Asian ancestry: a randomized controlled trial. BMC Med. 2018 Jul 10;16(1):104. doi: 10.1186/s12916-018-1093-8.

  PMID: 29986700 DERIVED

MeSH Terms

Interventions

Warfarin

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Boon Cher Goh, MBBS, MRCP

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Boon Cher Goh

CONTACT

65-6772-4617; Boon_Cher_Goh@nuhs.com.sg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Goh Boon Cher

Study Record Dates

• First Submitted: June 18, 2008
• First Posted: June 19, 2008
• Study Start: August 1, 2006
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2017
• Last Updated: June 7, 2016

Record last verified: 2016-06

Locations

SG (1); MY (1)