Midodrine in Hepatopulmonary Syndrome

January 5, 2021 updated by: Hilary M. DuBrock,, Mayo Clinic

A Phase 1 Proof-of-concept Clinical Trial Evaluating the Safety and Tolerability of Midodrine in Hepatopulmonary Syndrome

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.

Study Overview

Status

Completed

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Open Label
All 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.
Midodrine is an oral alpha-1 agonist that increases vascular tone. It is administered orally. 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability (adverse events (AEs))
Time Frame: 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.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Arterial Oxygenation
Time Frame: 3 months and 6 months

Describe the effect of midodrine on:

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

3 months and 6 months
Diffusion capacity
Time Frame: 3 months and 6 months

Describe the effect of midodrine on:

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

3 months and 6 months
Cardiac output
Time Frame: 3 months and 6 months
Describe the effect of midodrine on cardiac output (L/min) as estimated by echocardiogram in patients with HPS.
3 months and 6 months
Intrapulmonary shunting
Time Frame: 3 months and 6 months
Describe the effect of midodrine on severity (mild, moderate or severe) of intrapulmonary shunting (as assessed by echocardiogram shunt study) in patients with HPS.
3 months and 6 months
Intrapulmonary shunting
Time Frame: 6 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.
6 months
Symptoms as assessed by Modified Medical Research Council (MMRC)dyspnea scale
Time Frame: 3 months and 6 months
Describe the effect of midodrine on MMRC dyspnea scale (0-4). Higher numbers indicate more severe dyspnea.
3 months and 6 months
6 minute walk distance
Time Frame: 3 months and 6 months
Describe the effect of midodrine on 6 minute walk distance, in meters.
3 months and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Principal Investigator: Hilary M DuBrock, M.D., Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

August 2, 2018

Primary Completion (ACTUAL)

December 1, 2020

Study Completion (ACTUAL)

December 1, 2020

Study Registration Dates

First Submitted

June 20, 2018

First Submitted That Met QC Criteria

July 25, 2018

First Posted (ACTUAL)

July 26, 2018

Study Record Updates

Last Update Posted (ACTUAL)

January 6, 2021

Last Update Submitted That Met QC Criteria

January 5, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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