The Hemodynamic Effects of Vasopressin in Patients With Fontan Physiology

The goal of this study is to evaluate if vasopressin can elevate systemic arterial blood pressures without having a significant effect on pulmonary arterial pressures. Because patients who have undergone Fontan procedures rely on low pressures across the pulmonary vascular bed to maintain cardiac output, vasoactive agents that concomitantly increase systemic and pulmonary pressures may have a deleterious effect in this specific patient population.

Hypothesis: In patients with Fontan physiology, vasopressin will increase systemic BP by 20% above baseline, without increasing the transpulmonary gradient.

Study Overview

• Status: Completed
• Conditions: Hypotension; Fontan Physiology
• Intervention / Treatment: Drug: Vasopressin

Detailed Description

Patients with Fontan physiology are at increased risk of developing hypotension during periods of illness or with anesthesia. These patients have changes in venous capacitance, compliance, and venomotor tone. When hypotension occurs, the approach to management requires a careful understanding of these changes and the selection of appropriate, efficacious vasoactive agents. Vasoconstrictive medications are frequently used to treat hypotension when patients are refractory to fluid resuscitation. However, most of these medications have an effect on both the systemic and pulmonary circulations, raising the vascular pressures of both circuits. However, these patients often do not tolerate abrupt increases in pulmonary arterial pressures or vascular resistance, and a low transpulmonary gradient is imperative to maintain cardiac output. The ideal agent would be one that raises systemic vascular pressure while having a minimal effect on the pulmonary circulation.

One promising medication for treating hypotension in Fontan patients is vasopressin. One prior study evaluated the hemodynamic effect of vasopressin in pediatric patients with pulmonary hypertension. Compared to other vasopressor agents (phenylephrine, epinephrine), vasopressin increased systemic blood pressure with the least effect on pulmonary artery pressure. In a second study evaluating the use of vasopressin specifically for patients undergoing cardiac surgery for the creation of a Fontan, those who were treated with vasopressin as part of their postoperative management demonstrated lower transpulmonary gradients than those treated with placebo. Other studies have evaluated the use of vasopressin in Fontan patients for other clinical outcomes, such as decreasing postoperative chest tube output. On the basis of these studies, as well as our clinical experience managing these patients in the operating room, procedural suites, and in the intensive care unit, the investigator believes that vasopressin is not only safe but may be the preferred agent for this patient population.

Although vasopressin has been studied extensively in the context of sepsis, post cardiopulmonary bypass, and other vasoplegic disease states, the use of vasopressin has not yet been studied in the general population of patients who have Fontan physiology. The investigator hopes to demonstrate the efficacy of vasopressin as a medication specifically for these patients, as one that can elevate systemic blood pressure without compromising cardiac output or having a deleterious effect on the pulmonary vasculature.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University
    • Stanford, California, United States, 94305
      • Stanford University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. All patients scheduled for cardiac catheterization at Lucile Packard Children's Hospital with Fontan circulation

Exclusion criteria:

1. Critical illness severe enough to preclude extended cardiac catheterization time
2. Patients already on vasopressin
3. Patients with pulmonary hypertension.
4. Patient not scheduled for cardiac catheterization at Lucile Packard Children's Hospital (LPCH).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vasopressin; Participants undergoing cardiac catheterization	Drug: Vasopressin; Vasopressin administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in systemic (aortic) blood pressure		Pre-dose, every 5 minutes post-dose for approximately 15 minutes (post-baseline values will be averaged)
Change in pulmonary artery pressure		Pre-dose, every 5 minutes post-dose for approximately 15 minutes (post-baseline values will be averaged)
Change in transpulmonary gradient	Transpulmonary gradient = Mean pulmonary arterial pressure - left atrial pressure	Pre-dose, every 5 minutes post-dose for approximately 15 minutes (post-baseline values will be averaged)
PVR/SVR Ratio		Pre-dose, every 5 minutes post-dose for approximately 15 minutes (post-baseline values will be averaged)

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Manchula Navaratnam, MD, Stanford University

Publications and helpful links

General Publications

• Siehr SL, Feinstein JA, Yang W, Peng LF, Ogawa MT, Ramamoorthy C. Hemodynamic Effects of Phenylephrine, Vasopressin, and Epinephrine in Children With Pulmonary Hypertension: A Pilot Study. Pediatr Crit Care Med. 2016 May;17(5):428-37. doi: 10.1097/PCC.0000000000000716.
• Kumar TK, Kashyap P, Figueroa M, Zurakowski D, Allen J, Ballweg JA, Sathanandam S, Ali M, Knott-Craig CJ. Vasopressin After the Fontan Operation. World J Pediatr Congenit Heart Surg. 2016 Jan;7(1):43-8. doi: 10.1177/2150135115614574.
• Bigelow AM, Ghanayem NS, Thompson NE, Scott JP, Cassidy LD, Woods KJ, Woods RK, Mitchell ME, Hraska V, Hoffman GM. Safety and Efficacy of Vasopressin After Fontan Completion: A Randomized Pilot Study. Ann Thorac Surg. 2019 Dec;108(6):1865-1874. doi: 10.1016/j.athoracsur.2019.06.053. Epub 2019 Aug 7.
• Adamson GT, Yu J, Ramamoorthy C, Peng LF, Taylor A, Lennig M, Schmidt AR, Feinstein JA, Navaratnam M. Acute Hemodynamics in the Fontan Circulation: Open-Label Study of Vasopressin. Pediatr Crit Care Med. 2023 Nov 1;24(11):952-960. doi: 10.1097/PCC.0000000000003326. Epub 2023 Jul 18.

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2020
• Primary Completion (Actual): February 15, 2022
• Study Completion (Actual): February 15, 2022

Study Registration Dates

• First Submitted: June 29, 2020
• First Submitted That Met QC Criteria: July 3, 2020
• First Posted (Actual): July 9, 2020

Study Record Updates

• Last Update Posted (Actual): May 14, 2025
• Last Update Submitted That Met QC Criteria: May 11, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypotension; Physiological Effects of Drugs; Hemostatics; Coagulants; Natriuretic Agents; Vasoconstrictor Agents; Antidiuretic Agents; Vasopressins; Arginine Vasopressin
• Other Study ID Numbers: 56875

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes