Midodrine in Hepatopulmonary Syndrome
Primary Purpose
Hepatopulmonary Syndrome (HPS)
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Midodrine
Sponsored by
About this trial
This is an interventional treatment trial for Hepatopulmonary Syndrome (HPS)
Eligibility Criteria
Inclusion Criteria:
Moderate to very severe hepatopulmonary syndrome, defined as the presence of all of the following:
- Liver disease or portal hypertension
- Intrapulmonary shunting on contrast-enhanced echocardiogram
- 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
Sites / Locations
- Mayo Clinic in Rochester
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Open Label
Arm Description
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.
Outcomes
Primary Outcome Measures
Safety and tolerability (adverse events (AEs))
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
Arterial Oxygenation
Describe the effect of midodrine on:
• arterial oxygenation (PaO2 and A-a gradient )(mmHg)
Diffusion capacity
Describe the effect of midodrine on:
• percent predicted diffusion capacity for carbon monoxide (Range 0-100%)
Cardiac output
Describe the effect of midodrine on cardiac output (L/min) as estimated by echocardiogram in patients with HPS.
Intrapulmonary shunting
Describe the effect of midodrine on severity (mild, moderate or severe) of intrapulmonary shunting (as assessed by echocardiogram shunt study) in patients with HPS.
Intrapulmonary shunting
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 scale
Describe the effect of midodrine on MMRC dyspnea scale (0-4). Higher numbers indicate more severe dyspnea.
6 minute walk distance
Describe the effect of midodrine on 6 minute walk distance, in meters.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03600870
Brief Title
Midodrine in Hepatopulmonary Syndrome
Official Title
A Phase 1 Proof-of-concept Clinical Trial Evaluating the Safety and Tolerability of Midodrine in Hepatopulmonary Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
August 2, 2018 (Actual)
Primary Completion Date
December 1, 2020 (Actual)
Study Completion Date
December 1, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatopulmonary Syndrome (HPS)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Open Label
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Midodrine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety and tolerability (adverse events (AEs))
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Arterial Oxygenation
Description
Describe the effect of midodrine on:
• arterial oxygenation (PaO2 and A-a gradient )(mmHg)
Time Frame
3 months and 6 months
Title
Diffusion capacity
Description
Describe the effect of midodrine on:
• percent predicted diffusion capacity for carbon monoxide (Range 0-100%)
Time Frame
3 months and 6 months
Title
Cardiac output
Description
Describe the effect of midodrine on cardiac output (L/min) as estimated by echocardiogram in patients with HPS.
Time Frame
3 months and 6 months
Title
Intrapulmonary shunting
Description
Describe the effect of midodrine on severity (mild, moderate or severe) of intrapulmonary shunting (as assessed by echocardiogram shunt study) in patients with HPS.
Time Frame
3 months and 6 months
Title
Intrapulmonary shunting
Description
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.
Time Frame
6 months
Title
Symptoms as assessed by Modified Medical Research Council (MMRC)dyspnea scale
Description
Describe the effect of midodrine on MMRC dyspnea scale (0-4). Higher numbers indicate more severe dyspnea.
Time Frame
3 months and 6 months
Title
6 minute walk distance
Description
Describe the effect of midodrine on 6 minute walk distance, in meters.
Time Frame
3 months and 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Moderate to very severe hepatopulmonary syndrome, defined as the presence of all of the following:
Liver disease or portal hypertension
Intrapulmonary shunting on contrast-enhanced echocardiogram
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hilary M DuBrock, M.D.
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials
Learn more about this trial
Midodrine in Hepatopulmonary Syndrome
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