A Phase I Study of Stellate Ganglion Block and / or Reserpine in Group 2 Pulmonary Hypertension
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- Mayo Clinic
- 试验地点
- 1
- 主要终点
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
研究概览
简要总结
Pulmonary hypertension Group 2 (PH 2) associated with left-sided heart disease is relatively common, is associated with a poor prognosis, and unfortunately there are no proven medical treatments beyond attempts at correcting the left sided heart disease. Many PH 2 patients have evidence of active constriction of blood vessels from increased nerve traffic. Use of agents or procedures which produce a reversible chemical blockage of this nerve traffic have not been systematically tested in PH 2. The investigators will test whether acute interruption of sympathetic nervous system tone, which local anesthetic block of the stellate ganglion in the neck, will improve PH2, and also test whether the high blood pressure drug reserpine, which blocks sympathetic nerve activity, will do so during a one month trial period.
详细描述
Background. Pulmonary hypertension Group 2 (PH 2) associated with left-sided heart disease is relatively common, is associated with a poor prognosis, and unfortunately there are no proven medical treatments beyond attempts at correcting the left sided heart disease. Many PH 2 patients have evidence of vasoconstriction and increased sympathetic nervous system activity. Use of agents or procedures which produce a reversible chemical sympathectomy have not been systematically tested in PH 2.
Methods. Two groups will be eligible for participation: Group 1 (n=10): Patients with PH 2 previously documented by echocardiography (echo), 6 minute walk test, biomarkers, and right heart catheterization (RHC) will receive reserpine, 0.05 mg per day for two weeks, then, 0.1 mg per day for an additional two weeks. After one month, patients will be reassessed for New York Heart Association (NYHA) class and drug side effects, echocardiography, 6 minute walk assessment, and brain natriuretic peptide (BNP). Group 2 patients (n=10) will have clinically suspected PH 2 and be scheduled to undergo clinically indicated RHC. If during RHC PH 2 is confirmed, after assessment of nitric oxide responsiveness, their baseline hemodynamics will be re-established over 10 minutes, and a left stellate ganglion block with lidocaine will be performed, and immediate hemodynamic responsiveness assessed. Four hours post-procedure, a side effect questionnaire will be obtained. Group 2 patients who complete RHC will then begin reserpine treatment in the same manner as Group I patients.
Hypothesis and Impact. PH 2 is the most common type of pulmonary hypertension. The current diagnostic and therapeutic strategy aims to treat the left sided heart disease in attempt to normalize pulmonary artery pressure. The place of selective pulmonary vasodilators is undefined. The investigator's approach addresses inhibition of adverse pulmonary vasoconstriction mediated by the sympathetic nervous system in PH 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Prior right heart catheterization
Patients with qualifying hemodynamics from prior right heart catheterization will receive open label reserpine, 0.05 mg by mouth daily for two weeks, then 0.10 mg by mouth daily for two weeks, and then have repeat non-invasive assessments of status.
干预措施: reserpine (Drug)
Scheduled for right heart catheterization
Patients with suspected group 2 pulmonary hypertension by clinical and non-invasive assessments and are scheduled to undergo clinically indicated right heart catheterization will have pulmonary artery pressures measured. If qualifying severity of group 2 pulmonary hypertension is present, after clinically indicated assessment of inhaled nitric oxide, their baseline hemodynamics will be allowed to re-equilibrate over 10 minutes, and then ultrasound guided left stellate ganglion block with lidocaine will be performed, and hemodynamics reassessed 10 minutes afterward
干预措施: stellate ganglion block (Procedure)
Scheduled for right heart catheterization
Patients with suspected group 2 pulmonary hypertension by clinical and non-invasive assessments and are scheduled to undergo clinically indicated right heart catheterization will have pulmonary artery pressures measured. If qualifying severity of group 2 pulmonary hypertension is present, after clinically indicated assessment of inhaled nitric oxide, their baseline hemodynamics will be allowed to re-equilibrate over 10 minutes, and then ultrasound guided left stellate ganglion block with lidocaine will be performed, and hemodynamics reassessed 10 minutes afterward
干预措施: lidocaine (Drug)
结局指标
主要结局
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
时间窗: one month
Adverse events of interest are for stellate ganglion block: pulmonary edema, bradycardia requiring treatment, hypotension requiring treatment, arrhythmia, pneumothorax, hoarseness, dysphagia, globus, left upper extremity weakness. For reserpine, heart failure hospitalization, syncope, all cause hospitalization, bradycardia requiring treatment, hypotension requiring treatment, new arrhythmia, edema requiring an increase in diuretics, depression, lethargy, nasal stuffiness, dizziness, orthostatic hypotension, falls, nightmares, sexual dysfunction, anxiety, dyspepsia. Adverse events classed as serious: * Life threatening serious adverse events including acute coronary syndrome with active ischemia, fatal arrhythmias, myocardial infarction, acute kidney injury, cardiogenic shock, stroke, pulmonary embolization, arterial and/or venous thrombosis, systemic embolization, severe hypotension, respiratory failure and death * Prolonged hospitalization or rehospitalization
次要结局
- Effect of stellate ganglion block on heart rate(One hour)
- Change in 6 minute walk distance from one month of reserpine therapy(One month)
- Change in brain natriuretic peptide (BNP) from one month of reserpine therapy(One month)
- Change in Doppler derived mean pulmonary artery pressure from one month of reserpine therapy(One month)
- Change in blood pressure from one month of reserpine therapy(One month)
- Number of participants with successful stellate ganglion block(One hour)
- Change in Minnesota Living with heart failure questionnaire from one month of reserpine therapy(One month)
- Hemodynamic effect of stellate ganglion block(One hour)
- Change in heart rate from one month of reserpine therapy(One month)
研究者
Joseph L. Blackshear
Consultant, Department of Cardiovascular Diseases
Mayo Clinic