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

NCT02684786 | Withdrawn Phase 1

• 1 other identifier: 16-000928
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Artery Hypertension

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  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

  one month

Secondary Outcomes (13)

• Number of participants with successful stellate ganglion block

  One hour

• 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

Study Arms (2)

Prior right heart catheterization

EXPERIMENTAL

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.

Drug: reserpine

Scheduled for right heart catheterization

EXPERIMENTAL

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

Procedure: stellate ganglion block; Drug: lidocaine

Interventions

reserpine 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

Prior right heart catheterization

stellate ganglion block 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

Scheduled for right heart catheterization

lidocaine 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

Scheduled for right heart catheterization

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Familial Primary Pulmonary Hypertension

Interventions

Reserpine; Lidocaine

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Yohimbine; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Joseph Blackshear, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant, Department of Cardiovascular Diseases

Study Record Dates

• First Submitted: February 4, 2016
• First Posted: February 18, 2016
• Study Start: July 1, 2016
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: May 22, 2019

Record last verified: 2019-05

Locations

US (1)