The Impact of Aspirin Dose Modification on the Innate Immune Response - Will Lower Dose Aspirin Therapy Reduce the Response to Endotoxin
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Assess Inflammatory Response to Intravenous Endotoxin
研究概览
简要总结
Heart attacks are usually caused by clots in a coronary artery, depriving the heart muscle of blood. Platelets are the main type of blood cell causing clots to form and physicians typically give a combination of two anti-platelet drugs, aspirin and ticagrelor, to treat this. However, aspirin and ticagrelor have effects not just on the platelets but also on the immune system. The investigator has been investigating the effects of different doses of aspirin in heart attack participants when taken alongside ticagrelor, and have found that a new, lower dose of aspirin given twice daily, rather than the usual standard dose once daily, reduces the tendency to bleed whilst on treatment. The investigators are hoping to study the wider effects of different aspirin doses, with and without ticagrelor, and have therefore developed this study.
During the two periods of the study, the investigator will give healthy volunteers a combinations of these medications and then stimulate their immune system, in order to see if the medications affect the immune response. The study will involve a period of medication for 10-14 days followed by a day in hospital stimulating the immune system with an injection into the bloodstream of a substance known as endotoxin, which causes temporary flu-like symptoms, followed by blood and urine tests. The investigator will then repeat the process, after a minimum of five weeks, taking a different medication combination and having a further endotoxin injection. The investigator will also keep in contact by telephone until 2 weeks after the end of the medication to ensure participant remain well.
详细描述
Potential participants will contact the research team in response to advertisement. the research team will then set up a screening appointment in the Clinical Research Facility (CRF) at the Northern general Hospital. They will be offered the chance to be sent a copy of the Participant information sheet for the study before the screening appointment, otherwise they will receive on arrival to the CRF and will be given as much time as they would like to read this.
At the screening appointment (visit 1), a medically qualified member of the research team will discuss with the potential participant the background, rationale, design, requirements and risk of the study. The potential participant will have chance to ask any questions they wish and their understanding of the key points will be checked. If they are then happy to sign the consent form, they will do so and the medically-qualified members of the research team taking consent will also sign this. The participant will receive a copy of the signed form for their records. Once written consent has been obtained, participants will be interviewed to obtain information about their demographic details, medical history and medications. They will undergo a physical examination, have their vital signs and height/weight recorded, and have blood drawn from a vein for safety tests.
At visit 2, which should occur within 14 days of visit 1 but not before the results of the safety blood tests are known, ongoing consent, any new adverse events and medication changes will be recorded. Vital signs will be checked and physical examination performed. The research team will review the results of the safety blood tests and, in combination with information collected at visit 1, determine if the participant meets all the inclusion criteria and none of the exclusion criteria, and therefore whether they can proceed to randomisation, which will be performed using an electronic (online) system designed for this purpose, sealedenvelope.com.
Participants will be randomised to receive one of the following 8 treatment regimens, for 10 days, during the first period of the study:
- no drug
- Ticagrelor 180 milligrams (mg) as a loading dose on the last day
- Aspirin 20 mg BD
- Aspirin 20 mg BD, plus ticagrelor 180 mg as a loading dose on the last day
- Aspirin 75 mg once-daily (OD)
- Aspirin 75 mg, plus ticagrelor 180 mg as a loading dose on the last day
- Aspirin 300 mg OD
- Aspirin 300 mg OD, plus ticagrelor 180 mg as a loading dose on the last day
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
盲法说明
Masking is not applicable for this trial as this is an open label study.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male subjects, or female subjects not of childbearing potential (either surgically sterile or post-menopausal)]
- •Age between 18 and 65 years inclusive
- •Non-smokers
- •Body mass index (BMI) between 18 and 28 kg/m2 inclusive, with a body weight between 60-100 kg
- •In good health as determined by a medical history, physical examination, vital signs and clinical laboratory test results, including renal and liver function, and full blood count
- •Provision of informed consent before any trial-related activity
排除标准
- •Any history of cancer, diabetes or, in the opinion of the investigator, clinically-significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, haematological, dermatological, neurological, psychiatric or other major disorders
- •Any history of either significant multiple drug allergies or known allergy to the study drugs or any medicine chemically related to the study drugs
- •A clinically-significant illness within 4 weeks of randomisation
- •Any clinically-significant abnormal laboratory test results at screening in the opinion of the investigator
- •A supine blood pressure at screening, after resting for 5 minutes, higher than 150/90 mmHg or lower than 105/65 mmHg
- •A supine heart rate at screening, after resting for 5 minutes, outside the range of 50-100 beats/min
- •Receipt of any prescribed or over-the-counter systemic or topical medication within 48 hours prior to the start of dosing
- •Planned or expected requirement, during the next 3 months (at randomisation, or 3 weeks at the start of period 2), for any systemic or topical prescribed drug, or for systemic or topical over-the-counter NSAID, corticosteroid, anthihistamine or any other drug that could affect inflammation, thrombosis or haemostasis in the opinion of the investigator.
- •Receipt of an investigational medicinal product within the previous four months (new chemical entity) or three months (licensed product) or subjects who have received a vaccine within three weeks preceding the start of dosing. When reconfirming eligibility at the start of period 2, receipt of aspirin, ticagrelor or endotoxin during period 1 of this study will not be counted for this purpose.
- •Any donation of blood or plasma in the month preceding the start of dosing.
- •A history of alcohol or drug abuse
- •Mental incapacity or language barriers that preclude adequate understanding
研究组 & 干预措施
No Drug
Patients will be randomised to receive no drug for the first medication period (10 days).
Patient will then be allocated to receive ticagrelor 90mg twice daily for the second medication period (10 days)
干预措施: Ticagrelor (Drug)
Ticagrelor 180 mg
Participants will be randomised to receive loading dose of ticagrelor 180 mg on the last day of the first medication period (10-14 days).
Participants will then be allocated to receive no aspirin but a loading dose of ticagrelor 180 mg on the last day of treatment for the second medication period (10-14 days).
干预措施: Ticagrelor (Drug)
Aspirin 20mg
Participants will be randomised to receive aspirin 20 mg twice daily for the first medication period (10 days).
Participants will then be allocated to receive aspirin 20 mg twice daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period.
干预措施: Aspirin (Drug)
Aspirin 20mg
Participants will be randomised to receive aspirin 20 mg twice daily for the first medication period (10 days).
Participants will then be allocated to receive aspirin 20 mg twice daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period.
干预措施: Ticagrelor (Drug)
Aspirin 20 mg & Ticagrelor 180 mg
Participants will be randomised to receive aspirin 20 mg twice daily for the first medication period (10-14 days).
Participants will then be allocated to receive aspirin 20 mg twice daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period.
干预措施: Aspirin (Drug)
Aspirin 20 mg & Ticagrelor 180 mg
Participants will be randomised to receive aspirin 20 mg twice daily for the first medication period (10-14 days).
Participants will then be allocated to receive aspirin 20 mg twice daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period.
干预措施: Ticagrelor (Drug)
Aspirin 75 mg
Participants will be randomised to receive aspirin 75 mg once daily for the first medication period (10-14 days).
Participants will then be allocated to receive aspirin 75 mg once daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period.
干预措施: Aspirin (Drug)
Aspirin 75 mg
Participants will be randomised to receive aspirin 75 mg once daily for the first medication period (10-14 days).
Participants will then be allocated to receive aspirin 75 mg once daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period.
干预措施: Ticagrelor (Drug)
Aspirin 75 mg & Ticagrelor 180 mg
Participants will be randomised to receive aspirin 75 mg once daily for the first medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period.
Participants will then be allocated to receive aspirin 75 mg once daily for the second medication period (10-14 days).
干预措施: Aspirin (Drug)
Aspirin 75 mg & Ticagrelor 180 mg
Participants will be randomised to receive aspirin 75 mg once daily for the first medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period.
Participants will then be allocated to receive aspirin 75 mg once daily for the second medication period (10-14 days).
干预措施: Ticagrelor (Drug)
Aspirin 300 mg
Participants will be randomised to receive aspirin 300 mg once daily for the first medication period (10 days).
Participants will then be allocated to receive aspirin 300 mg once daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period.
干预措施: Aspirin (Drug)
Aspirin 300 mg
Participants will be randomised to receive aspirin 300 mg once daily for the first medication period (10 days).
Participants will then be allocated to receive aspirin 300 mg once daily for the second medication period (10-14 days), plus a loading dose of ticagrelor 180 mg on the last day of the period.
干预措施: Ticagrelor (Drug)
Aspirin 300 mg & Ticagrelor 180 mg
Participants will be randomised to receive aspirin 300 mg once daily for the first medication period (10-14 days) plus a loading dose of ticagrelor 180 mg on the last day of the period.
Participants will then be allocated to receive aspirin 300 mg once daily for the second medicaion period (10-14 days).
干预措施: Aspirin (Drug)
Aspirin 300 mg & Ticagrelor 180 mg
Participants will be randomised to receive aspirin 300 mg once daily for the first medication period (10-14 days) plus a loading dose of ticagrelor 180 mg on the last day of the period.
Participants will then be allocated to receive aspirin 300 mg once daily for the second medicaion period (10-14 days).
干预措施: Ticagrelor (Drug)
结局指标
主要结局
Assess Inflammatory Response to Intravenous Endotoxin
时间窗: 2 hours post endotoxin injection
plasma TNF-α at 2 hours post-injection of 2 ng/kg endotoxin compared between participants receiving no IMP, aspirin (Aspirin lysine) 20 mg BD, aspirin (Aspirin lysine) 75 mg OD and aspirin (Aspirin lysine) 300 mg OD.
次要结局
- Serum CRP Changes(0 to 6 hours after endotoxin administration)
- Leukocyte Count(0 to 6 hours after endotoxin administration)
- Serum TXB2(0 to 6 hours after endotoxin administration)