Midodrine in Hepatopulmonary Syndrome

Hepatopulmonary Syndrome (HPS) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03600870
• Other study ID #: 17-006221
• Status: Completed
• Phase: Phase 1
• Start date: August 2, 2018
• Est. completion date: December 1, 2020

Study information

• Verified date: January 2021
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: December 1, 2020
• Est. primary completion date: December 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatopulmonary Syndrome
• Hepatopulmonary Syndrome (HPS)
• Syndrome

Intervention

Drug:
• Midodrine
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.

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	Arterial Oxygenation	Describe the effect of midodrine on: • arterial oxygenation (PaO2 and A-a gradient )(mmHg)	3 months and 6 months
Secondary	Diffusion capacity	Describe the effect of midodrine on: • percent predicted diffusion capacity for carbon monoxide (Range 0-100%)	3 months and 6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	6 minute walk distance	Describe the effect of midodrine on 6 minute walk distance, in meters.	3 months and 6 months

External Links

•   Mayo Clinic Clinical Trials