Clinical trial NCT01633957: A Trial of Genotype-based Warfarin Initiation in Patients With Mechanical Prosthetic Heart Valve
Official title: Academic Leader，Head of Cardiac Surgery,Principal Investigator, Clinical Professor
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Anticoagulation Treatment Overdose
Heart Valve Diseases
Keywords: anticoagulation
bleeding
CYP2C9
CYP4F2
VKORC1
warfarin dosing
Heart Valve Diseases
pharmacogenomics
Lead sponsor: First Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Sun Yat-sen University
First posted: 2012-07-06
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Until very recently, warfarin is still the best drug of choice for long-term anticoagulation for patients with mechanical prosthetic heart valve. However, the complication of warfarin account for 75 percent of the whole complication after the mechanical prosthetic heart valve replacement.

Interindividual variation in warfarin dose is mediated by multiple factors.Advanced models using combinations of clinical attributes and genetic factors(CYP2C9, VKORC1, and CYP4F2) explain 50-75% of variability in warfarin dose requirements.These warfarin dosing models have the potential to improve patient safety by reducing or eliminating serious adverse events. The investigators conducted a prospective, randomized, blinded, two arm trial to test this hypothesis.


Eligibility criteria: Inclusion Criteria:

* the first time to receive elective mitral and/or aortic mechanical prosthetic valve replacement
* willing to join in the clinical trial and comply with the protocol.

Exclusion Criteria:

* other ethnic groups than Han
* previously receive any other cardiac surgery
* emergent surgery
* simultaneously carry out other cardiac surgeries,such as CABG
* age younger than 18y or older than 65 year
* drug abuser and wine abuser
* any malignancy
* moderate or severe hepatic or kidney insufficiency
* any thyroid disease
* the history of warfarin or VitK consumption 2 week before the surgery
* any hematological disease or history of bleeding
* combination with any drugs that significantly influence warfarin other than Cordarone
* pregnancy
* any contraindication of warfarin
* infectious endocarditis
* advanced valvular disease
* pathological obesity
* psychological disease
* any patient having joined in other clinical trial in the previous 30d
* basic INR \> 1.4

Primary outcomes:
measure: time to steady dosage
timeFrame: from seven days after the operation to thirty days after the operation
measure: Time in Therapeutic Range
timeFrame: from five days after the operation to thirty days after the operation
Secondary outcomes:
measure: first time to treatment window
timeFrame: from five days after the operation to thirty days after the operation
measure: the ratio of INR≥3.0 and INR≤1.5
timeFrame: from five days after the operation to thirty days after the operation
measure: the monitoring frequency of INR
timeFrame: 30 days after the operation
measure: the whole-cause mortality
timeFrame: 30 days after the operation
measure: major bleeding event
timeFrame: 30 days after the operation
measure: major thrombosis rate
timeFrame: 30 days after the operation
measure: absolute difference between the stable dose and initial dose
timeFrame: 30 days after the operation
measure: the frequency of dosage change
timeFrame: 30 days after the operation
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The first affiliated hospital of Sun Yat Sen University
state: Guangdong
Study officials:
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Xi Zhang, MD.
role: STUDY_DIRECTOR
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Zhe Xu, MD.,PHD.
role: PRINCIPAL_INVESTIGATOR
References: