Management of Acute Pulmonary Hypertensive Crisis in Children With Known Pulmonary Arterial Hypertension

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT05439460
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arms: 3
• Duration (Months): 29
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Pulmonary arterial hypertension (PAH) is a disease where the blood pressure in the pulmonary arteries (PAP) is high. PAH increases the risk of adverse events, including death, during and or after procedures. The severity of baseline PAH correlates with the incidence of major complications, such that those with PAP higher than their systemic blood pressure (SBP) had a 8 fold increased risk of complications. These children present for procedures where an acute exacerbation of their chronic illness-termed Pulmonary Hypertensive (PH)crisis, can occur, often resulting in death if not detected and managed expeditiously. Unfortunately there is little data and no consensus in the pediatric literature on how PH crisis should be managed.

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Condition or Disease	Intervention/Treatment	Phase
Pulmonary Arterial Hypertension	Drug: Phenylephrine; Drug: Epinephrine; Drug: Arginine Vasopressin	Phase 4

Detailed Description

Pulmonary arterial hypertension (PAH) is a disease where the blood pressure in the pulmonary arteries (PAP) is high. PAH increases the risk of adverse events, including death, during and or after procedures. The severity of baseline PAH correlates with the incidence of major complications, such that those with PAP higher than their systemic blood pressure (SBP) had a 8 fold increased risk of complications. These children present for procedures where an acute exacerbation of their chronic illness-termed PH crisis, can occur, often resulting in death if not detected and managed expeditiously. Unfortunately there is little data and no consensus in the pediatric literature on how PH crisis should be managed. Over the last 10 years we have developed considerable expertise in managing children with PAH and preventing and treating their acute crisis, using a medication called phenylephrine. This medication is routinely used to increase the blood pressure in patients (adults and children) to treat hypotension. Our theory has been that by increasing SBP, we can increase the blood flow to the coronary arteries and prevent the right ventricle from failing acutely. The latter results in catastrophic hypotension, heart arrythmias and death. There is no consensus or protocol guiding the management of the acute crisis. This purpose of this study is to close that gap.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Management of Acute Pulmonary Hypertensive Crisis in Children With Known Pulmonary Arterial Hypertension
• Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phenylephrine Phenylephrine will be administered once the child is under anesthesia and the interventional cardiologist has measured the pressures in the pulmonary artery.	Drug: Phenylephrine; 5 subjects will get Phenylephrine during cardiac catheterization in patient with known Pulmonary Arterial Hypertension.Dose will be 1ug/kg body weight. Pressures in the pulmonary artery will be measured before and after the drug administration.; Other Names: Phenylephrine Hydrochloride
Experimental: Epinephrine Epinephrine will be administered once the child is under anesthesia and the interventional cardiologist has measured the pressures in the pulmonary artery.	Drug: Epinephrine; 5 subjects will get Epinephrine during cardiac catheterization in patient with known Pulmonary Arterial Hypertension.Dose will be 0.5-1ug/kg body weight. Pressures in the pulmonary artery will be measured before and after the drug administration.; Other Names: Epinephrine injection
Experimental: Arginine Vasopressin Arginine Vasopressin will be administered once the child is under anesthesia and the interventional cardiologist has measured the pressures in the pulmonary artery.	Drug: Arginine Vasopressin; 5 subjects will get Arginine Vasopressin during cardiac catheterization in patient with known Pulmonary Arterial Hypertension.Dose will be 1ug/kg body weight. Pressures in the pulmonary artery will be measured before and after the drug administration.; Other Names: Vasopressin injection

Outcome Measures

Primary Outcome Measures

1. Change in Systemic Vascular Resistance Index (SVRI) to Pulmonary Vascular Resistance Index (PVRI) Ratio (Rp:Rs Ratio) [Day 1 (at baseline and up to 5 minutes following study drug administration) (Q: 2 minutes - 2 to 5 minutes?)]

   In patients with pulmonary hypertension (PH) one anticipates a greater increase in pulmonary vascular resistance as opposed to systemic vascular resistance when vasopressors are administered.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients presenting for cardiac catheterization procedure with a diagnosis of PAH either by previous cardiac catheterization or echocardiography

Exclusion Criteria:

• Children presenting for cardiac catheterization who do not have PAH;

• Children with PAH but with intracardiac shunts

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cardiac Catheterization Lab,Stanford University Medical Center	Stanford	California	United States	94043

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Chandra Ramamoorthy, MD, Cardiac Anesthesia, Stanford University Medical Ctr.

Study Documents (Full-Text)

• Study Protocol - Nov 8, 2011
• Statistical Analysis Plan - May 1, 2016

More Information

Publications

• Friesen RH, Williams GD. Anesthetic management of children with pulmonary arterial hypertension. Paediatr Anaesth. 2008 Mar;18(3):208-16. doi: 10.1111/j.1460-9592.2008.02419.x. Review.

• Responsible Party: Chandra Ramamoorthy, Professor, Pediatric Cardiac Anesthesia, Stanford University
• ClinicalTrials.gov Identifier: NCT05439460
• Other Study ID Numbers: 22554
• First Posted: Jun 30, 2022
• Last Update Posted: Aug 5, 2022
• Last Verified: Jul 1, 2022

• 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.: No
• Additional relevant MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension; Phenylephrine; Vasopressins; Arginine Vasopressin; Epinephrine; Racepinephrine; Oxymetazoline; Epinephryl borate

Study Results

Participant Flow

Pre-assignment Detail	Participants were assigned sequentially; the first group received phenylephrine, the second group received arginine vasopressin, and the third group received epinephrine.

Arm/Group Title	Phenylephrine	Arginine Vasopressin	Epinephrine
Arm/Group Description	Phenylephrine (1ug/kg) administered once the child is under anesthesia.	Arginine Vasopressin (1ug/kg) administered once the child is under anesthesia.	Epinephrine (0.5-1ug/kg) administered once the child is under anesthesia.
Period Title: First Intervention (Approx 5h on Study)
STARTED	5	0	0
COMPLETED	5	0	0
NOT COMPLETED	0	0	0
Period Title: First Intervention (Approx 5h on Study)
STARTED	0	5	0
COMPLETED	0	5	0
NOT COMPLETED	0	0	0
Period Title: First Intervention (Approx 5h on Study)
STARTED	0	0	5
COMPLETED	0	0	5
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Phenylephrine	Arginine Vasopressin	Epinephrine	Total
Arm/Group Description	Phenylephrine (1ug/kg) administered once the child is under anesthesia.	Arginine Vasopressin (1ug/kg) administered once the child is under anesthesia.	Epinephrine (0.5-1ug/kg) administered once the child is under anesthesia.	Total of all reporting groups
Overall Participants	5	5	5	15
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.2 (3.8)	10.5 (4.9)	6.8 (4.2)	9.2 (4.5)
Sex: Female, Male (Count of Participants)
Female	4 80%	4 80%	3 60%	11 73.3%
Male	1 20%	1 20%	2 40%	4 26.7%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
United States	5 100%	5 100%	5 100%	15 100%

Outcome Measures

1. Primary Outcome

Title	Change in Systemic Vascular Resistance Index (SVRI) to Pulmonary Vascular Resistance Index (PVRI) Ratio (Rp:Rs Ratio)
Description	In patients with pulmonary hypertension (PH) one anticipates a greater increase in pulmonary vascular resistance as opposed to systemic vascular resistance when vasopressors are administered.
Time Frame	Day 1 (at baseline and up to 5 minutes following study drug administration) (Q: 2 minutes - 2 to 5 minutes?)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phenylephrine	Arginine Vasopressin	Epinephrine
Arm/Group Description	Phenylephrine (1ug/kg) administered once the child is under anesthesia.	Arginine Vasopressin (1ug/kg) administered once the child is under anesthesia.	Epinephrine (0.5-1ug/kg) administered once the child is under anesthesia.
Measure Participants	5	5	5
Baseline	0.8 (0.7)	0.75 (0.41)	0.61 (0.23)
Approx. 2 minutes following drug administration	0.73 (0.77)	0.49 (0.24)	0.6 (0.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Phenylephrine
	Comments	Change in phenylephrine group
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9
	Comments
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Arginine Vasopressin
	Comments	Change in arginine vasopressin group
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3
	Comments	A p-value of <0.05 would be considered statistically significant.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Epinephrine
	Comments	Change in epinephrine group
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	1
	Comments	A p-value of <0.05 would be considered statistically significant.
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	During procedure (approx. 5 h)
Arm/Group Title	Phenylephrine		Arginine Vasopressin		Epinephrine
Arm/Group Description	Phenylephrine (1ug/kg) administered once the child is under anesthesia.		Arginine Vasopressin (1ug/kg) administered once the child is under anesthesia.		Epinephrine (0.5-1ug/kg) administered once the child is under anesthesia.
All Cause Mortality
	Phenylephrine		Arginine Vasopressin		Epinephrine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		0/5 (0%)
Serious Adverse Events
	Phenylephrine		Arginine Vasopressin		Epinephrine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Phenylephrine		Arginine Vasopressin		Epinephrine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/5 (0%)		2/5 (40%)
Cardiac disorders
Transient arrhythmia	0/5 (0%)		0/5 (0%)		2/5 (40%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.