A Study of Stellate Ganglion Block and / or Reserpine in Group 2 Pulmonary Hypertension

NCT ID: NCT02684786

Last Updated: 2019-05-22

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2016-07-31

Brief Summary

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.

Detailed Description

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.

Conditions

Pulmonary Artery Hypertension

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

reserpine

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

stellate ganglion block

Intervention Type: PROCEDURE

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

lidocaine

Intervention Type: DRUG

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

Interventions

reserpine

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

Intervention Type: DRUG

stellate ganglion block

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

Intervention Type: PROCEDURE

lidocaine

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Prior right heart catheterization, with mean pulmonary artery pressure > 25 mm Hg, pulmonary capillary wedge pressure > 15 mm Hg, and diastolic pressure gradient (pulmonary artery diastolic pressure - mean pulmonary capillary wedge pressure) ≥ 7 mm Hg OR clinically suspected group 2 pulmonary hypertension from non-invasive testing with planned right heart catheterization (RHC).
• On stable diuretic therapy
• Able to attend end-study visit 4 weeks after study entry

Exclusion Criteria

• Anticipated surgery to correct heart lesion responsible for pulmonary hypertension
• Need for heparinization for right heart catheterization (not standard practice, but sometimes utilized)
• History of depression, or treatment with tricyclic anti-depressant, serotonin uptake inhibitor, monamine oxidase inhibitor
• Severe renal or hepatic impairment, creatinine clearance < 30 ml/minute or renal replacement therapy or post-kidney transplant, abnormal liver function with elevated enzymes> 1.5 times the upper limit of normal or prior liver transplant.
• Systolic blood pressure <100 mm Hg
• Heart rate < 60 beats per minute
• Inability to independently complete telephone follow-up at two weeks, and clinic end-study visit at 4 weeks.
• Pulmonary edema
• Infiltrative cardiomyopathy - amyloidosis
• Symptomatic orthostatic hypotension
• Women of childbearing age who have not had surgical sterilization and are not using oral contraceptives, or who's spouse has not had surgical sterilization will be excluded due to the length of the trial and the possibility that they could become pregnant after entry.
• Uncontrolled heartburn
• Prior surgery to the left neck, for example, carotid endarterectomy, or other surgery which would increase the risk of stellate ganglion block
• Known sensitivity, allergy, or contraindication to lidocaine, any local anesthetic, or reserpine

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Joseph L. Blackshear

Consultant, Department of Cardiovascular Diseases

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joseph Blackshear, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic Florida

Jacksonville, Florida, United States

Countries

United States

Related Links

https://www.mayo.edu/research/clinical-trials

Mayo Clinic Clinical Trials

Other Identifiers

16-000928

Identifier Type: -

Identifier Source: org_study_id