search
Back to results

Effect of Genes on Rosuvastatin Therapy for Hyperlipidemia

Primary Purpose

Hyperlipidemia

Status
Available
Phase
Locations
Study Type
Expanded Access
Intervention
rosuvastatin,fenofibrate
CYP2C9, UGT1A1, UGT1A3, OATP2, BCRP
Sponsored by
National Taiwan University Hospital
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an expanded access trial for Hyperlipidemia focused on measuring genes, rosuvastatin, fenofibrate, Cardiovascular (CV) diseases, dyslipidemia, metabolic syndrome, identify genetic determinants of the wide range of interindividual variability in phenotypic and clinical response to the lipid-lowering drug classes, identify genetic susceptibility to drug-related side effects.

Eligibility Criteria

20 Years - 79 Years (Adult, Older Adult)All Sexes

Inclusion Criteria:

  • Men or women aged 20-79 years with definite DM or atherosclerotic vascular diseases with metabolic syndrome, defined as the presence of three or more of the following risk factors:

    • abdominal obesity (waist circumference > 90 cm in men or > 80 cm in women),
    • triglycerides > 150 mg/dL, HDL-cholesterol < 40 mg/dL in men or < 50 mg/dL in women,
    • blood pressure > 130/85 mm Hg, or
    • fasting glucose > 100 mg/dL).
  • Those who are qualified for lipid lowering therapy according to the Taiwanese national guidelines (LDL-C 130-190 mg/dL or TG 200-500 mg/dL with HDL-C < 40 mg/dL or TC/HDL-C > 5).

Exclusion Criteria:

  • Any known contraindications to statin or fibrate therapy,
  • Previous intolerance to statin or fibrate in low or high doses,
  • Liver enzyme levels more than 3 times the upper limit of normal,
  • Pregnancy or breastfeeding,
  • Nephrotic syndrome,
  • Uncontrolled diabetes mellitus (HbA1c > 9),
  • Uncontrolled hypothyroidism,
  • Plasma LDL-C level higher than 190 mg/dL or triglyceride level higher than 500 mg/dL,
  • Coronary heart disease event or revascularisation within a month,
  • Congestive heart failure (New York Heart Association classification IIIb or IV),
  • Hemodynamically important valvular heart disease,
  • Gastrointestinal conditions affecting absorption of drugs,
  • Treatment with other drugs that seriously affect the pharmacokinetics of statins or fibrate,
  • Unexplained creatine phosphokinase concentrations six or more times the upper limit of normal,
  • Life-threatening malignancy,
  • Treatment with immuno suppressive or other lipid lowering drugs.
  • Patients previously treated with monotherapy with statins or fibrates will be qualified if they have not already had titration to a dose higher than the equivalent of 5 mg/d of rosuvastatin or 160 mg/d of SFC fenofibrate.

Sites / Locations

    Outcomes

    Primary Outcome Measures

    Secondary Outcome Measures

    Full Information

    First Posted
    July 6, 2009
    Last Updated
    December 20, 2012
    Sponsor
    National Taiwan University Hospital
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT00934258
    Brief Title
    Effect of Genes on Rosuvastatin Therapy for Hyperlipidemia
    Official Title
    Effect of Genes on Rosuvastatin Therapy for Hyperlipidemia
    Study Type
    Expanded Access

    2. Study Status

    Record Verification Date
    November 2012
    Overall Recruitment Status
    Available
    Study Start Date
    undefined (undefined)
    Primary Completion Date
    undefined (undefined)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    National Taiwan University Hospital

    4. Oversight

    5. Study Description

    Brief Summary
    Previous studies indicate that the variant status of detoxification proteins is different among Taiwanese and other ethnic groups. For example, in Taiwanese, the major SNPs of CYP2C9 are CYP2C9*2 (430C>T) and CYP2C9*3 (1075A>C) and their frequencies are different from that in Caucasians [11]. The second example is that the frequency of the A(TA)7TAA allele in the promoter area of the UGT1A1 gene is substantially lower, while for the rate of variation within the coding region is much higher in Taiwanese than that in Caucasians (14.3% vs. 35.7- 41.5% and 29.3% vs. 0.1%, respectively) [12]. The third example is that the frequency of 388A>G of the OATP2 gene in Taiwanese (0.68) [13] is in between that in European Americans (0.30) and African Americans (0.74) [14]. Therefore, the investigators hypothesize that, in Taiwanese the SNPs of detoxification proteins modulate the lipid-lowing effects of RVA and fenofibrate may be different from those for Caucasians.
    Detailed Description
    Since April 2008, we have started to run a multicenter, prospective, randomized, open-label, blinded end-point classification trial to test the hypothesis in Taiwan that the addition of fibrate on statin would provide a further reduction in the major coronary events in the patients with diabetes or atherosclerotic vascular diseases with metabolic syndrome. With the advantage of this large-scaled prospective trial, it is also a good opportunity to identify simultaneously the genetic determinants of wide range of interindividual variability in phenotypic and clinical response to two major lipid-lowering drug classes, rosuvastatin and fenofibrate. The aim of this proposal is to find which SNPs influence the therapeutic effectiveness of lipid lowering therapy in Taiwanese hyperlipidemic patients. A key feature is the use of multiple drug-treated population samples to get the findings derived from both candidate gene and genome-wide searches for SNP associations with markers of drug efficacy as well as side effects. Thus the promise of pharmacogenomics and metabolomics-- "individualized medicine" will come true in treating hyperlipidemia in Taiwanese.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Hyperlipidemia
    Keywords
    genes, rosuvastatin, fenofibrate, Cardiovascular (CV) diseases, dyslipidemia, metabolic syndrome, identify genetic determinants of the wide range of interindividual variability in phenotypic and clinical response to the lipid-lowering drug classes, identify genetic susceptibility to drug-related side effects.

    7. Study Design

    8. Arms, Groups, and Interventions

    Intervention Type
    Drug
    Intervention Name(s)
    rosuvastatin,fenofibrate
    Intervention Description
    Rosuvastatin 10 mg once daily Rosuvastatin 5 mg + SFC fenofibrate 80 mg
    Intervention Type
    Genetic
    Intervention Name(s)
    CYP2C9, UGT1A1, UGT1A3, OATP2, BCRP
    Intervention Description
    All potential patients will be screened for the eligibility in a screening visit. Those who fill the inclusion criteria at screening will be invited for the registry study into different groups. The follow-up will take place at months 6, 12, 18, and every year thereafter for another 3 years, through clinical visiting, phone follow-up, or records from the NHIB Taiwan. At each clinical visit, vital signs, clinical endpoints, adverse events, concurrent medication information and laboratory specimens will be obtained as complete as possible. With phone or records from NHIB, only clinical endpoints will be recorded. If the primary care physician intends to treat the patient's lipid profile to the target, he/she can add, delete or adjust the LLT by his/her clinical judgement

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    20 Years
    Maximum Age & Unit of Time
    79 Years
    Eligibility Criteria
    Inclusion Criteria: Men or women aged 20-79 years with definite DM or atherosclerotic vascular diseases with metabolic syndrome, defined as the presence of three or more of the following risk factors: abdominal obesity (waist circumference > 90 cm in men or > 80 cm in women), triglycerides > 150 mg/dL, HDL-cholesterol < 40 mg/dL in men or < 50 mg/dL in women, blood pressure > 130/85 mm Hg, or fasting glucose > 100 mg/dL). Those who are qualified for lipid lowering therapy according to the Taiwanese national guidelines (LDL-C 130-190 mg/dL or TG 200-500 mg/dL with HDL-C < 40 mg/dL or TC/HDL-C > 5). Exclusion Criteria: Any known contraindications to statin or fibrate therapy, Previous intolerance to statin or fibrate in low or high doses, Liver enzyme levels more than 3 times the upper limit of normal, Pregnancy or breastfeeding, Nephrotic syndrome, Uncontrolled diabetes mellitus (HbA1c > 9), Uncontrolled hypothyroidism, Plasma LDL-C level higher than 190 mg/dL or triglyceride level higher than 500 mg/dL, Coronary heart disease event or revascularisation within a month, Congestive heart failure (New York Heart Association classification IIIb or IV), Hemodynamically important valvular heart disease, Gastrointestinal conditions affecting absorption of drugs, Treatment with other drugs that seriously affect the pharmacokinetics of statins or fibrate, Unexplained creatine phosphokinase concentrations six or more times the upper limit of normal, Life-threatening malignancy, Treatment with immuno suppressive or other lipid lowering drugs. Patients previously treated with monotherapy with statins or fibrates will be qualified if they have not already had titration to a dose higher than the equivalent of 5 mg/d of rosuvastatin or 160 mg/d of SFC fenofibrate.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    chau-chung Wu, Phd
    Phone
    +886-2-23123456
    Ext
    65428
    Email
    chauchungwu@ntu.edu.tw

    12. IPD Sharing Statement

    Learn more about this trial

    Effect of Genes on Rosuvastatin Therapy for Hyperlipidemia

    We'll reach out to this number within 24 hrs