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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open Label | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Midodrine | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Arterial Oxygenation | Describe the effect of midodrine on: • arterial oxygenation (PaO2 and A-a gradient )(mmHg) | 3 months and 6 months |
| Diffusion capacity | Describe the effect of midodrine on: • percent predicted diffusion capacity for carbon monoxide (Range 0-100%) |
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Inclusion Criteria:
Moderate to very severe hepatopulmonary syndrome, defined as the presence of all of the following:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Hilary M DuBrock, M.D. | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic in Rochester | Rochester | Minnesota | 55905 | United States |
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| Label | URL |
|---|---|
| Mayo Clinic Clinical Trials | View source |
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| ID | Term |
|---|---|
| D020065 | Hepatopulmonary Syndrome |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D008879 | Midodrine |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| 3 months and 6 months |
| Cardiac output | 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 | 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 | 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 | 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 | Describe the effect of midodrine on 6 minute walk distance, in meters. | 3 months and 6 months |
| D000588 |
| Amines |