Cardiac Arrhythmia Catheter Ablation Procedures Guided by x-Ray Imaging: N-Acetylcysteine Protection Against Radiation Induced Cellular damagE (CARAPACE Study)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 181
- 试验地点
- 1
- 主要终点
- Measurement of change in systemic oxidative stress (ratio between GSH oxidized form (GSSG) and GSH, 8-iso-prostaglandinF2α (8-iso-PGF2α) and 8-hydroxy-2-deoxyguanosine (8-OHdG)) and genomic DNA oxidative damage (percentage of DNA present in the tails).
研究概览
简要总结
Catheter ablation procedures (CAPs) are first line treatment for a great variety of cardiac arrhythmias. CAPs require X-Ray imaging; consequently, CAPs cause ionizing radiation (IR) exposure for patients. Exposure to IR, even at low-doses, increases individual risk of developing cancer. IR cause DNA damage directly and, mostly, indirectly by formation of cellular free radicals. Furthermore different response to IR results from inherited variants in genes involved in DNA damage repair. N-acetylcysteine (NAC) is an aminoacid that can directly neutralize free radicals and increase antioxidant systems. Our preliminary data suggest that IR exposure in patients undergoing CAP deranges the oxidative stress status and the pre-procedure intravenous administration of NAC could decrease such abnormality.
详细描述
CARAPACE is a prospective, randomized, single-blinded, parallel-arm monocenter study. Eligible patients undergoing CAP at the Arrhythmology Unit of Centro Cardiologico Monzino will be enrolled.
The hypothesis driving our study, based on published literature and our preliminary data, is that administration of antioxidant agents, before cardiac procedures involving IR exposure, might prevent IR harmful effects on human tissues in terms of reduction of systemic oxidative stress status and, in parallel, of oxidative DNA damage.
The antioxidant agent tested in our study is NAC. NAC is a well-tolerated and safe medication and it has antioxidant properties is based on three main mechanisms: 1) direct antioxidant effect, 2) glutathione (GSH) precursor action, and 3) its activity in breaking thiolated proteins.
Another hypothesis to be tested is whether genes involved in DNA damage repair could explain the great variability in patient radiosensitivity to IR exposure and whether these genes could affect NAC protective/healing effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Researchers, involved in the assessment of NAC efficacy, are blinded to randomization process; thus, they do not know whether the patients are in the NAC or in the control groups.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient's age >18 years.
- •Negative hCG pregnancy test (if appropriate).
- •Indication to perform CAP guided by fluoroscopy (IR imaging).
- •Ability and willingness to give informed consent and to comply with protocol.
排除标准
- •Any contraindication to CAP (such as, pregnancy and breastfeeding).
- •Hypersensitivity to the active substance or to any of the excipients.
- •Enrollment in another study that may interfere with CARAPACE study.
- •Administration of an experimental drug within 30 days or 5 half-lives of the investigational drug.
- •Chronic kidney disease (serum creatinine >1.5 mg/dl).
- •Acute/Chronic inflammatory disease.
- •Antioxidant drugs intake over the previous 2 weeks.
- •History of radiotherapy or chemotherapy in the last year.
- •Any documented condition that, in PI's motivated judgement, makes the patient a poor candidate for the study.
- •Computed tomography and/or coronary angiography within 5 days prior to baseline analysis.
研究组 & 干预措施
Pharmacological treatment
Patients are treated with NAC prior to carrying out CAP.
干预措施: Acetyl cysteine (Drug)
结局指标
主要结局
Measurement of change in systemic oxidative stress (ratio between GSH oxidized form (GSSG) and GSH, 8-iso-prostaglandinF2α (8-iso-PGF2α) and 8-hydroxy-2-deoxyguanosine (8-OHdG)) and genomic DNA oxidative damage (percentage of DNA present in the tails).
时间窗: 48 hours
Measurement of change in systemic oxidative stress (GSSG/GSH, 8-iso-PGF2α and 8-OHdG) and genomic DNA oxidative damage (% DNA present in the tails of the comet assay) between the two groups (NAC versus no NAC) at the different time-points (T0 = before CAP, T1 = 3h after CAP, T2 = 24h after CAP, T3 = 48h after CAP).
次要结局
- Measurement of change in systemic oxidative stress (GSSG/GSH, 8-iso-PGF2α and 8-OHdG) and genomic DNA oxidative damage (% DNA present in the tails) related to IR dose (fluoroscopy time (FT), Dose Area Product (DAP) and effective dose (ED)).(48 hours)
- Measurement of change in genomic DNA oxidative damage (% DNA present in the tails) related to IR dose (FT, DAP and ED) and inherited variants in genes involved in DNA damage repair.(48 hours)
- Measurement of change in the response to NAC administration related to inherited variants in genes involved in DNA damage repair.(48 hours)
研究者
Claudio Tondo
Deputy of Heart Rhythm Center
Centro Cardiologico Monzino