Improving Right Ventricular Function in Young Adults Born Preterm

NCT03696758 | Completed Phase 2 Results FDA Drug

• 5 other identifiers: 2018-07961UL1TR002373-01A534285SMPH/MEDICINE/PULMON MEDProtocol Version 8/30/2018
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Infant,Premature

Keywords

premature adults; premature; premature cardiac function; MRI; sildenafil; metoprolol; CMR

Outcome Measures

Primary Outcomes (2)

• Right Ventricular Energetic Efficiency Pre and Post Metoprolol

  To characterize energy efficiency, the total Kinetic Energy across the cardiac cycle is normalized to right ventricular end-diastolic volume and left ventricular end-diastolic volume, respectively. Analysis will be completed in blinded fashion. Two imaging scans will be done - one pre and one post Metoprolol intervention. Total time from Pre-intervention scan till post intervention scan may take up to 2 hours.

  up to 2 hours

• Right Ventricular Energetic Efficiency Pre and Post Sildenafil

  To characterize energy efficiency, the total Kinetic Energy across the cardiac cycle is normalized to right ventricular end-diastolic volume and left ventricular end-diastolic volume, respectively. Analysis will be completed in blinded fashion. Two imaging scans will be done - one pre and one post Sildenafil intervention. Total time from Pre-intervention scan till post intervention scan may take up to 2 hours.

  up to 2 hours

Secondary Outcomes (18)

• Left Ventricular Energetic Efficiency Pre and Post Metoprolol

  up to 2 hours

• Right Ventricular Ejection Fraction Pre and Post Metoprolol

  up to 2 hours

• Right Ventricular Stroke Volume Pre and Post Metoprolol

  up to 2 hours

• Right Ventricular Systolic Volume Pre and Post Metoprolol

  up to 2 hours

• Right Ventricular Diastolic Volume Pre and Post Metoprolol

  up to 2 hours

Study Arms (2)

Sildenafil followed by Metoprolol

EXPERIMENTAL

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.

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

Metoprolol followed by Sildenafil

EXPERIMENTAL

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.

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

Interventions

Pulmonary Function Testing PROCEDURE

Subjects will undergo spirometry, Plethysmography, and diffusion capacity.

Metoprolol followed by Sildenafil; Sildenafil followed by Metoprolol

Electrocardiogram PROCEDURE

Subjects will undergo an electrocardiogram to ensure sinus rhythm

Metoprolol followed by Sildenafil; Sildenafil followed by Metoprolol

Cardiac Magnetic Resonance Imaging PROCEDURE

Subjects will undergo positron magnetic resonance imaging to detect images of the heart

Metoprolol followed by Sildenafil; Sildenafil followed by Metoprolol

Metoprolol DRUG

Subjects will receive intravenous metoprolol. Dose titrated 1-5 mg every 2 minutes to achieve goal heart rate of 55-65 beats per minute, or for subjects with a resting heart rate already at goal, titrated to achieve a 10-15% reduction in heart rate.

Also known as: Lopressor, Metolar XR

Metoprolol followed by Sildenafil; Sildenafil followed by Metoprolol

Sildenafil DRUG

Subjects will receive a 50 milligram tablet of sildenafil (to be taken orally)

Also known as: Revatio

Metoprolol followed by Sildenafil; Sildenafil followed by Metoprolol

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated informed consent form
• Male or female aged 18-35
• History of preterm birth (either a or b):
• Participant in the Newborn Lung Project (birth year 1988-1991, birth weight \<1500 g)
• Non-NLP participant, with birth weight \<1500 g and gestational age 32 weeks or less, verified by medical records

You may not qualify if:

• Pregnant or lactating
• Use of prescribed medications that would interfere with study medications
• Sildenafil: Use of phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil), nitrates, soluble guanylate cyclase inhibitor (riociguat) within 48 hours of study visit
• Metoprolol: Use of nodal blocking agents including beta blockers, non-dihydropyridine calcium channel blockers (i.e. diltiazem), and anti-arrhythmics (i.e. amiodarone)
• Presence of known comorbidities for which these therapeutic interventions would be contraindicated:
• Moderate to severe heart failure
• Severe bradycardia (heart rate \<45), or second or third-degree heart block
• Systolic blood pressure \<90 mmHg or \>190 mmHg
• Angina
• Severe peripheral arterial circulatory disorders
• History of severe bronchospasm
• Presence of any implanted device incompatible with CMR imaging
• Known allergic or hypersensitivity reaction to components of the study medications
• Any other reason for which the investigator deems a subject unsafe or inappropriate for study participation.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

University of Wisconsin-Madison School of Medicine and Public Health

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Premature Birth

Interventions

Respiratory Physiological Phenomena; Metoprolol; Sildenafil Citrate

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Circulatory and Respiratory Physiological Phenomena; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Sulfonamides; Amides; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Kara Goss
• Organization: UT Southwestern, Dallas, Texas

kara.goss@utsouthwestern.edu

214-648-6868

Study Officials

• Kara N Goss, MD

  University of Wisconsin-Madison School of Medicine and Public Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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 a separate visit. These visits can occur in either order. There will be a minimum period of 12 hours between drug interventions to ensure adequate drug wash-out.

Study Record Dates

• First Submitted: October 3, 2018
• First Posted: October 5, 2018
• Study Start: October 30, 2018
• Primary Completion: February 24, 2020
• Study Completion: February 24, 2020
• Last Updated: March 17, 2021
• Results First Posted: February 25, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)