Improving Right Ventricular Function in Young Adults Born Preterm

University of Wisconsin (UW)

Status and phase: Completed; Phase 2

Conditions: Infant,Premature

Treatments: Procedure: Pulmonary Function Testing; Procedure: Cardiac Magnetic Resonance Imaging; Drug: Sildenafil; Drug: Metoprolol; Procedure: Electrocardiogram

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03696758

SMPH/MEDICINE/PULMON MED (Other Identifier)

A534285 (Other Identifier)

Protocol Version 8/30/2018 (Other Identifier)

2018-0796

1UL1TR002373-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The purpose of this research is to evaluate the short-term effects of sildenafil and metoprolol on heart function in young adults born premature.

Full description

The purpose of this study is to evaluate the short-term therapeutic effects of sildenafil and metoprolol on right ventricular function in young adults born premature using novel 4-Dimensional flow Cardiac Magnetic Resonance Imaging.

Enrollment: 10 patients

Sex: All

Ages: 18 to 35 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Provision of signed and dated informed consent form

2. Male or female aged 18-35

3. History of preterm birth (either a or b):

   1. Participant in the Newborn Lung Project (birth year 1988-1991, birth weight <1500 g)
   2. Non-NLP participant, with birth weight <1500 g and gestational age 32 weeks or less, verified by medical records

Exclusion criteria

1. Pregnant or lactating

2. Use of prescribed medications that would interfere with study medications

   1. Sildenafil: Use of phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil), nitrates, soluble guanylate cyclase inhibitor (riociguat) within 48 hours of study visit
   2. Metoprolol: Use of nodal blocking agents including beta blockers, non-dihydropyridine calcium channel blockers (i.e. diltiazem), and anti-arrhythmics (i.e. amiodarone)

3. Presence of known comorbidities for which these therapeutic interventions would be contraindicated:

   1. Moderate to severe heart failure
   2. Severe bradycardia (heart rate <45), or second or third-degree heart block
   3. Systolic blood pressure <90 mmHg or >190 mmHg
   4. Angina
   5. Severe peripheral arterial circulatory disorders
   6. History of severe bronchospasm

4. Presence of any implanted device incompatible with CMR imaging

5. Known allergic or hypersensitivity reaction to components of the study medications

6. Any other reason for which the investigator deems a subject unsafe or inappropriate for study participation.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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10 participants in 2 patient groups

Sildenafil followed by Metoprolol

Experimental group

Description:

Young adults born premature, recruited either from the National Lung Project Cohort or the general public, will undergo Cardiac Magnetic Resonance Imaging before and after medication administration. This will occur twice, on two separate visits. Subjects will be given sildenafil in between imaging scans at one visit, and will receive intravenous metoprolol in between scans at next visit. There will be a minimum period of 12 hours between drug interventions to ensure adequate drug wash-out. Subjects will also undergo pulmonary function testing and electrocardiogram.

Treatment:

Procedure: Pulmonary Function Testing

Drug: Metoprolol

Procedure: Electrocardiogram

Drug: Sildenafil

Procedure: Cardiac Magnetic Resonance Imaging

Metoprolol followed by Sildenafil

Experimental group

Description:

Young adults born premature, recruited either from the National Lung Project Cohort or the general public, will undergo Cardiac Magnetic Resonance Imaging before and after medication administration. This will occur twice, on two separate visits. Subjects will be given metoprolol in between imaging scans at one visit, and will receive intravenous sildenafil in between scans at next visit. There will be a minimum period of 12 hours between drug interventions to ensure adequate drug wash-out. Subjects will also undergo pulmonary function testing and electrocardiogram.

Treatment:

Procedure: Pulmonary Function Testing

Drug: Metoprolol

Procedure: Electrocardiogram

Drug: Sildenafil

Procedure: Cardiac Magnetic Resonance Imaging