NCT04297241

Brief Summary

The investigators will investigate the safety and preliminary efficacy of ISDN therapy to reduce venous congestion and improve exercise tolerance in children and adults after the Fontan operation. This will be accomplished by recruiting 15 Fontan physiology patients from the Cincinnati Children's Fontan clinic and University of Kentucky Pediatric Cardiology clinic for the investigation. The investigators will non-invasively measure both central venous pressures at rest and during graded cardiopulmonary exercise testing. In addition the study team will obtain a measurement of liver stiffness before and after a 4-week regimen of ISDN therapy. Patients will be seen twice in clinic, once before and after ISDN therapy, and phone calls will be made to ensure safety, compliance, and make appropriate alterations to medications throughout the study period. Pre- and post-intervention central venous pressure and exercise tolerance will be compared.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Dec 2019

Shorter than P25 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 12, 2019

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

February 5, 2020

Completed
29 days until next milestone

First Posted

Study publicly available on registry

March 5, 2020

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2020

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 3, 2021

Completed
4 months until next milestone

Results Posted

Study results publicly available

August 25, 2021

Completed
Last Updated

September 22, 2021

Status Verified

July 1, 2021

Enrollment Period

7 months

First QC Date

February 5, 2020

Results QC Date

July 9, 2021

Last Update Submit

August 25, 2021

Conditions

Outcome Measures

Primary Outcomes (1)

  • Number of Participants Who Experience an Adverse Reaction to the Study Medication During the Study Enrollment Period.

    Potential adverse side effects of study medication (isosorbide dinitrate) will be monitored throughout study period. Study medication will be titrated to a maximal dose of 30mg dependent on the patient tolerance. Patient tolerance is defined by frequency of known risk factors to the study medication (headaches, hypotension, and syncope).

    Baseline and 6 weeks

Secondary Outcomes (5)

  • Effect of Isosorbide Dinitrate on Liver Stiffness Levels

    Baseline and 6 weeks

  • Effect of Isosorbide Dinitrate on Central Venous Pressure

    Baseline and 6 weeks

  • Effect of Isosorbide Dinitrate on Maximal Exercise Capacity VO2 Max

    Baseline and 6 weeks

  • Effect of Isosorbide Dinitrate on Maximal Exercise Capacity Heart Rate Response

    Baseline and 6 weeks

  • Effect of Isosorbide Dinitrate on Maximal Exercise Capacity Respiratory Rate Response

    Baseline and 6 weeks

Study Arms (1)

Isosorbide Dinitrate

EXPERIMENTAL

Each enrolled participant will be on a titrated dosage of isosorbide dinitrate to determine effectiveness on both primary and secondary outcome measures.

Drug: Isosorbide Dinitrate

Interventions

All patients will be given a 6 week titration regimen of study medication. Patients will begin at a 5mg dosage and titrate up to 30mg three times per day if each subsequent dose is tolerated.

Also known as: Isordil
Isosorbide Dinitrate

Eligibility Criteria

Age9 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Underlying Fontan physiology
  • On a stable medication regimen for the past 3 months
  • Nine years of age or older

You may not qualify if:

  • Pregnant or nursing
  • Prior hospitalization for heart failure in past year
  • Presence of uncontrolled arrhythmias within the past 6 months
  • Non-cardiac conditions which significantly limited exercise
  • Moderate or severe ventricular dysfunction by echocardiogram or cardiac MRI
  • Currently treated with a phosphodiesterase-5 inhibitor or organic nitrates
  • Concurrent enrollment in other investigational drug trial
  • End stage Liver Disease (ESLD)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (1)

  • Bigelow AM, Riggs KW, Morales DLS, Opotowsky AR, Lubert AM, Dillman JR, Veldtman GR, Heydarian HC, Trout AT, Cooper DS, Goldstein SL, Chin C, Palermo JJ, Ollberding NJ, Mays WA, Alsaied T. Isosorbide DiNitrate Effect on Hemodynamic Profile, Liver Stiffness, and Exercise Tolerance in Fontan Circulation (The NEET Clinical Trial). Pediatr Cardiol. 2024 Oct;45(7):1389-1397. doi: 10.1007/s00246-023-03156-3. Epub 2023 Apr 21.

MeSH Terms

Interventions

Isosorbide Dinitrate

Intervention Hierarchy (Ancestors)

IsosorbideSorbitolSugar AlcoholsAlcoholsOrganic ChemicalsCarbohydrates

Results Point of Contact

Title
Mary Banks
Organization
Cincinnati Children's Hospital

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 5, 2020

First Posted

March 5, 2020

Study Start

December 12, 2019

Primary Completion

June 30, 2020

Study Completion

May 3, 2021

Last Updated

September 22, 2021

Results First Posted

August 25, 2021

Record last verified: 2021-07

Data Sharing

IPD Sharing
Will not share

Locations