Asprin Dosing Estimator in Healthy Adults
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 57
- 试验地点
- 1
- 主要终点
- Height
研究概览
简要总结
Understanding sources of variability in human drug dosing is important to the beneficial and safe use of any drug. Understanding and applying the science of individualizing a drug dose to a patient is called precision medicine.
Aspirin is one of the oldest most utilized medications for its ability to lower fever, relieve pain, and to reduce the stickiness of platelets (tiny blood cells that help your body form clots to stop bleeding. Aspirin dosing is currently the same for all patients and is not individualized. In the last century, aspirin has shown benefit in reducing cancer, stroke, and preventing cardiovascular events after one has already had a heart attack or stroke. Previous human studies have not found consistent positive effects of aspirin when dosed by body weight. Therefore, how should aspirin be dosed in 2019? Aspirin resistance is the failure of aspirin to reduce platelet stickiness and thin the blood and most importantly, is associated with higher risk of heart attacks and strokes. Aspirin resistance may occur due to not taking aspirin on a regular basis, differences in how platelets behave in some persons, use of over the counter pain medicines like Motrin®, reduced amount of drug in the body, and/or a lack of being able to predict a dose for a certain individual.
To find out the best way to dose aspirin, the investigators propose to study healthy volunteers (persons without any known disease) with different ages and body sizes to see if aspirin blood levels are tied to platelet stickiness. This information will be used to mathematically build a computer-based picture of aspirin dosing that will help physicians pick the best dose of aspirin for each patient. The investigators will then extend studies for the aspirin dose estimator to be used in other countries in people with heart problems and stroke, recording future events in a randomized (i.e., coin toss) manner, to determine if the ability of the aspirin dose estimator to prevent future heart attacks and stroke compared to people receiving aspirin doses that were chosen without the estimator.
详细描述
AIM 1: Determine urine TXB2, platelet aggregation function testing (VerifyNow® ASA Test), salicylate level, CBC with differential, and hs-CRP, in 18 healthy volunteers across BMI classes of 22-25 (Normal Weight), >25-30 (Overweight), and > 30 kg/m2 (Obese).Total enrolled cohort: 60 patients and planned treatment cohort: 54 completed patients (anticipated dropout rate of 10% = 6 patients). The investigators have powered this sample size based on estimates of effect sizes from published studies examining platelet activation in patients across a range of BMIs and assuming an alpha = 0.05, with 80% power. In addition, height and weight as predictors will be evaluated independently of BMI. BMI patient groups (22-25, >25-30, and > 30 kg/m2) will be randomized to low-dose ASA (81mg standard-release), moderate dose ASA (325mg) or high dose ASA (500mg) (6 patients/each dose).
All patients will have a CBC with differential (to measure blood cell counts including platelets) and hs-CRP at baseline, serial urine TXB2 (-1, and 2 and 5 hours post ASA dose), platelet aggregation function testing using VerifyNow® ASA Test 15 min post ASA dose, serial salicylate levels (0, 15", 2 hours post-ASA dose) and again 10-14 days after chronic dosing (urine TXB2 2 hours post ASA dose and platelet aggregation function testing using VerifyNow® Test 15 min post ASA dose only).
AIM 2: Model associations between construct variables (BMI and aspirin dose) with predictive variables as collected in AIM 1. Multiple and Linear Regression with backward selection will be used. In addition, a Structured Equation Model will be applied to the data. Statistical assessment of model fit will be conducted for all models.
AIM 3: Build an Aspirin Dose Estimator to predict aspirin dosing. Model associations from AIM 2 will create demand estimates that will feed into a user-friendly aspirin dosage estimator. The simulator will comprise: 1) Entry: An entry screen. In this screen the user will enter the features of patient clinical information attributes. The user then clicks a 'run' button. 2) Demand Output: The simulator will then create an output screen that will show graphically aspirin dosing options.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Ages 18-55 years old (male or female)
- •Healthy Volunteers (medication free without acute or chronic significant health problems or pathologies)
排除标准
- •History of asthma
- •History of chronic bronchitis
- •History of emphysema
- •History of renal impairment (eGFR < 30 ml/min)
- •History of hypertension (reviewed by study staff)
- •History of hyperlipidemia
- •History of diabetes
- •History of smoking (within last month)
- •Current depression or anxiety requiring medication therapy
- •Inability to finish the study for any reason
- •Any current pathological condition outside of normal range
- •Thrombocytopenia (platelet count < 150 K/µL)
- •Other known platelet disorders (eg. von Willebrand disease, Glanzmann thrombasthenia, Bernard-Soulier Syndrome)
- •Current use of dipyradamole, PGY 12 inhibitors, NSAIDs
- •Or as otherwise determined by the investigative team
研究组 & 干预措施
Obese/Normal Dose Aspirin
BMI 25-30 kg/m^2 & receiving 325mg Aspirin daily for 2 weeks
干预措施: Aspirin (Drug)
Normal Weight/Low Dose Aspirin
BMI 22-25 kg/m^2 & receiving 81mg Aspirin daily for 2 weeks
干预措施: Aspirin (Drug)
Normal Weight/Normal Dose Aspirin
BMI 25-30 kg/m^2 & receiving 325mg Aspirin daily for 2 weeks
干预措施: Aspirin (Drug)
Normal Weight/High Dose Aspirin
BMI > 30 kg/m^2 & receiving 500mg Aspirin daily for 2 weeks
干预措施: Aspirin (Drug)
Overweight/Low Dose Aspirin
BMI 22-25 kg/m^2 & receiving 81mg Aspirin daily for 2 weeks
干预措施: Aspirin (Drug)
Overweight/Normal Dose Aspirin
BMI 25-30 kg/m^2 & receiving 325mg Aspirin daily for 2 weeks
干预措施: Aspirin (Drug)
Overweight/High Dose Aspirin
BMI > 30 kg/m^2 & receiving 500mg Aspirin daily for 2 weeks
干预措施: Aspirin (Drug)
Obese/Low Dose Aspirin
BMI 22-25 kg/m^2 & receiving 81mg Aspirin daily for 2 weeks
干预措施: Aspirin (Drug)
Obese/High Dose Aspirin
BMI > 30 kg/m^2 & receiving 500mg Aspirin daily for 2 weeks
干预措施: Aspirin (Drug)
结局指标
主要结局
Height
时间窗: 2 weeks per participant
Used to measure BMI
Urine TBX2 Collection (Thromboxane levels)
时间窗: 2 weeks per participant
Thromboxane levels measured for indicator of platelet aggregation function
Aspirin Reaction Units (ARU)
时间窗: 2 weeks per participant
Number given from Verifynow device that will be used to determine platelet aggregation function by arachidonic acid induced aggregation
Weight
时间窗: 2 weeks per participant
Used to measure BMI
Salicylate Levels
时间窗: 2 weeks per participant
Used to measure amount of systemic aspirin to compare with TBX2 and BMI categories
次要结局
- High-sensitivity C-reactive protein (hs-CRP)(2 weeks per participant)
- Blood Pressure (mmHg)(2 weeks per participant)
- Complete Blood Count (CBC)(2 weeks per participant)
- Heart Rate (BPM)(2 weeks per participant)
- Respiratory Rate (breaths per minute)(2 weeks per participant)
研究者
mark munger
Principal Investigator
University of Utah