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Midodrine in Hepatopulmonary Syndrome

Phase 1
Completed
Conditions
Hepatopulmonary Syndrome (HPS)
Interventions
Registration Number
NCT03600870
Lead Sponsor
Mayo Clinic
Brief Summary

This proof-of-concept clinical trial will determine the safety and tolerability of midodrine in patients with hepatopulmonary syndrome (HPS). Exploratory endpoints will assess the effect of midodrine on oxygenation, intrapulmonary shunting and symptoms.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
10
Inclusion Criteria
  • Moderate to very severe hepatopulmonary syndrome, defined as the presence of all of the following:

    1. Liver disease or portal hypertension
    2. Intrapulmonary shunting on contrast-enhanced echocardiogram
    3. Hypoxemia [A-a gradient ≥15mmHg (or ≥20mmHg if age >64) and PaO2<80mmHg on arterial blood gas testing]
  • Ability to provide informed consent

  • Ability to comply with study medication use and testing, in the opinion of the principal investigator or co-investigator

Exclusion Criteria
  • Vulnerable study population, including imprisoned individuals, non-English speaking patients
  • Participation in other investigational drug studies
  • Any of the following conditions:
  • Systolic blood pressure>160mmHg or diastolic blood pressure >100mmHg
  • Heart rate <50bpm
  • Urinary retention at baseline
  • Left ventricular ejection fraction <50%
  • Women who are pregnant, nursing, or who plan to become pregnant while in the trial
  • Women of child-bearing potential not willing or able to use highly effective methods of birth control

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Open LabelMidodrineAll subjects enrolled will be assigned to receive midodrine. The initial starting dose will be midodrine 5mg orally three times a day. After 7-10 days, patients will increase the dose to 10mg three times a day as tolerated if no adverse effects occur. Treatment duration will be 6 months.
Primary Outcome Measures
NameTimeMethod
Safety and tolerability (adverse events (AEs))6 months

Outcome will be defined by the incidence of adverse events (AEs) that occur during the study period. An adverse event is defined as any symptom, sign, illness or experience that develops or worsens in severity during the course of the study. Abnormal results of diagnostic procedures are considered to be AEs if the abnormality results in study withdrawal, is associated with a serious AE, is associated with clinical signs or symptoms, leads to additional treatment or further diagnostic tests or is considered by the investigator to be of clinical significance. Each adverse event will be further characterized by severity and relationship to the study drug. Adverse event are classified as serious if they are: fatal, life-threatening, require or prolongs hospital stay, lead to persistent or significant disability or incapacity or a congenital anomaly or birth defect.

Secondary Outcome Measures
NameTimeMethod
Cardiac output3 months and 6 months

Describe the effect of midodrine on cardiac output (L/min) as estimated by echocardiogram in patients with HPS.

Arterial Oxygenation3 months and 6 months

Describe the effect of midodrine on:

• arterial oxygenation (PaO2 and A-a gradient )(mmHg)

Diffusion capacity3 months and 6 months

Describe the effect of midodrine on:

• percent predicted diffusion capacity for carbon monoxide (Range 0-100%)

Intrapulmonary shunting6 months

Describe the effect of midodrine on severity of intrapulmonary shunting (as assessed by percent shunt index (0-100%) on technetium macroaggregated albumin scan) in patients with HPS.

Symptoms as assessed by Modified Medical Research Council (MMRC)dyspnea scale3 months and 6 months

Describe the effect of midodrine on MMRC dyspnea scale (0-4). Higher numbers indicate more severe dyspnea.

6 minute walk distance3 months and 6 months

Describe the effect of midodrine on 6 minute walk distance, in meters.

Trial Locations

Locations (1)

Mayo Clinic in Rochester

🇺🇸

Rochester, Minnesota, United States

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