The Anti-Anginal Effects of N-Acetylcysteine (NAC) in Patients with Angina and Non-Obstructive Coronary Arteries (ANOCA)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Frequency of angina episodes recorded in angina diary.
研究概览
简要总结
The goal of this clinical trial is to determine if N-acetylcysteine (NAC) can reduce angina frequency in women with Angina with Non-Obstructive Coronary Arteries (ANOCA). It will also assess the impact of NAC on health status and quality of life. The main questions it aims to answer are:
(i) Does NAC reduce the number of angina episodes per week? (ii) How does NAC affect quality of life and symptom burden in ANOCA patients? (iii) Does NAC reduce the need for short-acting nitrate use?
Researchers will compare NAC to a placebo in a randomized, double-blind, placebo-controlled crossover study to determine its effectiveness.
Participants will receive treatment with NAC 600mg twice daily for 4 weeks (28 days) and matched placebo for 4 weeks (28 days) in a computer-generated random order giving a total dosing period of 8 weeks. There will be a 2-week washout between the two treatment periods.
The effectiveness of N-Acetylcysteine (NAC) will be assessed using the following measures:
Angina Diary: Participants will record the frequency and severity of their angina episodes.
Seattle Angina Questionnaire-7 (SAQ-7): Participants will complete this questionnaire to assess physical limitations, angina frequency, and quality of life.
EuroQol 5-Dimension (EQ-5D) Questionnaire: Participants will rate their overall health and quality of life.
详细描述
Background:
Angina with Non-Obstructive Coronary Arteries (ANOCA) refers to a condition where patients experience chronic angina despite having no significant coronary artery blockages. This condition affects 50-70% of women undergoing elective angiography, in stark contrast to just 7-17% of men. Many experience a prolonged delay in diagnosis, resulting in notable decreases in functional capacity.
NAC has been shown to reduce oxidative stress and potentiate the vasodilatory and antiaggregatory effects of nitrates, potentially reducing microvascular damage and improving myocardial perfusion, hence presenting a promising therapeutic option for ANOCA patients. Although there are no established clinical guidelines for ANOCA management, standard therapy typically includes both long-acting and short-acting nitrates to alleviate anginal symptoms. However, many ANOCA patients continue to experience symptoms despite standard therapy. As such, this trial will assess the beneficial effects of NAC therapy in ANOCA women.
Primary Objectives: To determine the effect of NAC 600mg twice daily on angina frequency in patients with ANOCA who experience angina at least 3 times/week as assessed by an angina diary.
Secondary Objective: The secondary objectives of this study are:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Statistician
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Provision of informed consent prior to any study specific procedures
- •Female patients aged ≥18 years
- •No obstructive CAD (defined as either absence of epicardial lesions with ≥50% luminal narrowing in any coronary artery segment on coronary angiography or normal findings on computed tomography (CT) angiogram, indicating the absence of significant stenosis) to account for chest pain symptoms.
- •Chest pain occurring ≥3 times/week in the preceding two weeks.
排除标准
- •Known allergy to NAC or its components.
- •Acute myocardial infarction admission within the preceding month (hospital admission for prolonged angina paint associated with a cardiac troponin level above the 99th percentile, with a subsequent rise or fall).
- •Secondary causes of angina including:
- •i. clinically significant anaemia (haemoglobin <100g/dL) ii. uncontrolled atrial fibrillation (ventricular response rate >108bpm) iii. haemodynamically significant aortic stenosis (mean valve gradient ≥40mmHg) d) Known concomitant disease with life expectance of less than 1 year. e) Abnormalities in liver function tests suggesting hepatic impairment (ALT and/or AST 2 x upper limit of normal (ULN) or ALP 2 x ULN or Bilirubin 1.5 x ULN) f) Severe renal impairment (eGFR <30mL/min) or on dialysis. g) Pregnancy or lactation. h) Untreated hypertension i) Unwilling, or unable, to give informed consent, including due to severe psychiatric conditions affecting informed consent process or compliance.
- •j) History of substance abuse. k) Currently taking Chloroquine. l) Serious or unstable medical conditions that may interfere with the study, as determined by the PI.
- •m) Concomitant participation in another clinical trial or research study (except where in the opinion of the PI, the participant could benefit from enrolling in another trial)
研究组 & 干预措施
Oral NAC 600mg (twice daily) Intervention Arm
This arm will assess the effects of oral N-Acetylcysteine (NAC) at a dose of 600mg twice daily in patients with ANOCA. Participants will receive the NAC treatment for a 4-week period.
干预措施: N-Acetylcysteine (NAC) (Drug)
Placebo 600mg twice daily
This arm will serve as the placebo comparator in the crossover study design. Participants will receive a placebo treatment that is identical in appearance to the NAC medication but contains no active ingredient.The order of treatment (NAC vs placebo) is randomized and participants remain blinded throughout the study.
干预措施: Placebo (Drug)
结局指标
主要结局
Frequency of angina episodes recorded in angina diary.
时间窗: 8 weeks (4 weeks of NAC treatment and 4 weeks of placebo treatment)
Number of angina episodes recorded in angina diary. The angina diary is developed to record the frequency, duration, severity, and reliever of chest pain episodes. Participant record their angina episodes throughout the study period.
次要结局
- Frequency of Short-acting nitrate consumption (i.e., Glyceryl trinitrate (GTN) spray use)(8 weeks (4 weeks treatment compared to 4 weeks placebo))
- Frequency of prolonged angina episodes (ie episodes persisting > 20 minutes)(8 weeks (4 weeks of NAC treatment and 4 weeks of placebo treatment))
- Angina frequency score as assessed by Seattle Angina Questionnaire (SAQ)(End of Phase 1 (Score at the end of 4 weeks) & End of Phase 2 ( Score at the end of 4 weeks))
- Angina-related physical limitations score as assessed on Seattle Angina Questionnaire(End of Phase 1 (Score at the end of 4 weeks) & End of Phase 2 ( Score at the end of 4 weeks))
- Angina-related quality of life score as assessed on Seattle Angina Questionnaire(End of Phase 1 (Score at the end of 4 weeks) & End of Phase 2 ( Score at the end of 4 weeks))
- Patient satisfaction with angina therapy score as assessed on Seattle Angina Questionnaire(End of Phase 1 (Score at the end of 4 weeks) & End of Phase 2 ( Score at the end of 4 weeks))
- Overall physical health as assessed by EQ-5D Questionnaire(End of Phase 1 (Score at the end of 4 weeks) & End of Phase 2 ( Score at the end of 4 weeks))
- Severity score of angina episodes as assessed on angina diary(8 weeks (4 weeks of NAC treatment and 4 weeks of placebo treatment))
研究者
Sivabaskari Pasupathy
Post doctoral Research Fellow
University of Adelaide