Prevention of Dialysis-Induced Hypotension by Inhibiting Plasma Kallikrein
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Blood Pressure during hemodialysis
研究概览
简要总结
Bradykinin is a potent vasodilator that is formed by the activation of the kallikrein-kinin system. We and others have shown that bradykinin increased during hemodialysis; however, the role of bradykinin in dialysis-induced hypotension (DIH) has not been evaluated. Preliminary results from a pilot clinical trial showed that bradykinin B2 receptor blockade with icatibant prevents excessive blood pressure during hemodialysis. Thus, in this study, we will test the overarching hypothesis that blockade plasma kallikrein with lanadelumab would ameliorate the reduction of blood pressure during hemodialysis in patients who are prone to DIH. For this purpose, we will conduct a parallel arm, double-blind placebo-controlled trial, using lanadelumab to evaluate the occurrence of
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects age 18 to 85 years
- •On thrice-weekly hemodialysis for at least six months
- •Clinically stable, adequately dialyzed (single-pool Kt/V > 1.2), with polysulphone membrane for at least three consecutive months before the study
- •Subjects with pre-dialytic systolic blood pressure between 110 and 170 mmHg.
- •Subjects with a reduction of systolic blood pressure during hemodialysis equal to or greater than 30 mmHg, with associated symptoms such as nausea, vomiting, muscle cramps, dizziness, or anxiety.
- •Hypotensive episodes should occur four times or more in four weeks (12 hemodialysis sessions).
排除标准
- •Subjects with intradialytic hypotension that require the use of pharmacological intervention such as midodrine or vasopressin
- •Subjects with pre-dialytic systolic blood pressure greater than 170 mmHg or diastolic blood pressure greater than 110 mmHg
- •History of myocardial infarction or cerebrovascular event within 3 months
- •History of serious hemorrhage (including cerebral hemorrhage) in the past 6 months
- •Advanced liver disease
- •Ejection fraction less than 30%
- •Anticipated live donor kidney transplant
- •A history of poor adherence to hemodialysis or medical regimen
- •Severe anemia (hemoglobin less than 8 g/dl) requiring blood transfusions
- •Use of immunosuppressive drugs within one month before study enrollment
- •Active connective tissue disease
- •History of acute infections disease within one month before study enrollment
- •Inability to provide consent
- •Pregnancy
研究组 & 干预措施
Placebo
Subjects will receive placebo subcutaneously at the beginning of the study and 14 days later
干预措施: Placebo (Drug)
Lanadelumab
Subjects will receive lanadelumab (300 mg) subcutaneously at the beginning of the study and 14 days later
干预措施: Lanadelumab Injection [Takhzyro] (Drug)
结局指标
主要结局
Blood Pressure during hemodialysis
时间窗: From the second week of the study until the end (week 6)
Average blood pressure during hemodialysis of three hemodialysis sessions after the second week of treatment.
Blood Pressure During Hemodialysis
时间窗: Pre-hemodialysis and post-hemodialysis, up to 4.5 hours, at baseline and at the end of the study (week 6)
Systolic blood pressure pre and post hemodialysis at baseline and at the end of the study
次要结局
- Hypotensive episodes(From the second week of the study until the end (week 6))
- Hypotensive Episodes(From the first week of the study until the end (week 6))
- Episodes(From the first week of the study until the end (week 6))
研究者
Jorge Gamboa
Research Assistant Professor
Vanderbilt University Medical Center