PRIMaCY: PRecIsion Medicine in CardiomyopathY

• Sponsor: The Hospital for Sick Children (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04036799
• Collaborator: Stanford University (Other), Children's Hospital of Philadelphia (Other), New York Presbyterian Hospital (Other), University of Texas Southwestern Medical Center (Other), University of Michigan (Other), Children's Hospital Medical Center, Cincinnati (Other), Provincial Health Services Authority (Other), Stollery Children's Hospital (Other), Children's Hospital of Eastern Ontario (Other), The Royal Children's Hospital Melbourne (Other), Children's Healthcare of Atlanta (Other), Primary Children's Hospital (Other), Medical University of South Carolina (Other), Boston Children's Hospital (Other), Baylor College of Medicine (Other), The Cleveland Clinic (Other), Monroe Carell Jr. Children's Hospital at Vanderbilt (Other), Children's Hospital Colorado (Other), Indiana University Health (Other), OHSU Doernbecher Children's Hospital (Other), Children's Hospital Los Angeles (Other)
• Enrollment: 572
• Anticipated Duration (Months): 83

Study Details

Study Description

Brief Summary

This is a retrospective cohort study of pediatric hypertrophic cardiomyopathy (HCM) patients using chart and registry review methodology. The studies objective is to develop and validate a sudden cardiac death (SCD) risk calculator that is age-appropriate for children with HCM that includes clinical and genetic factors.

Condition or Disease	Intervention/Treatment	Phase
Hypertrophic Cardiomyopathy; Sudden Cardiac Death

Study Design

• Study Type: Observational
• Actual Enrollment: 572 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Development of a Risk Calculator to Predict Sudden Cardiac Death in Children With Hypertrophic Cardiomyopathy
• Actual Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Jun 1, 2020
• Anticipated Study Completion Date: Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Hypertrophic Cardiomyopathy

Outcome Measures

Primary Outcome Measures

1. Number of Participants With a Composite Sudden Cardiac Death Event [Time to a composite sudden cardiac death event during 5-year follow-up]

   The composite SCD event includes post diagnosis SCD, aborted SCD (including ventricular fibrillation, sustained ventricular tachycardia), primary ICD insertion with appropriate shock, secondary ICD insertion

Eligibility Criteria

Criteria

• Ages Eligible for Study: 0 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• phenotype-positive patients diagnosed with hypertrophic cardiomyopathy

• phenotype-negative, genotype positive patients considered at risk for developing hypertrophic cardiomyopathy

Exclusion Criteria:

• Neuromuscular, metabolic, syndromic (other than Noonan Syndrome and related RAS-opathies) or endocrine (including infants of diabetic mothers) causes of HCM

• (Other treatable causes of left ventricular hypertrophy (systemic hypertension, anatomic defects causing left ventricular outflow tract obstruction e.g. aortic stenosis, subAS, subaortic membrane, coarctation)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• The Hospital for Sick Children
• Stanford University
• Children's Hospital of Philadelphia
• New York Presbyterian Hospital
• University of Texas Southwestern Medical Center
• University of Michigan
• Children's Hospital Medical Center, Cincinnati
• Provincial Health Services Authority
• Stollery Children's Hospital
• Children's Hospital of Eastern Ontario
• The Royal Children's Hospital Melbourne
• Children's Healthcare of Atlanta
• Primary Children's Hospital
• Medical University of South Carolina
• Boston Children's Hospital
• Baylor College of Medicine
• The Cleveland Clinic
• Monroe Carell Jr. Children's Hospital at Vanderbilt
• Children's Hospital Colorado
• Indiana University Health
• OHSU Doernbecher Children's Hospital
• Children's Hospital Los Angeles

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Nov 30, 2018
• Statistical Analysis Plan - Jul 21, 2020

More Information

Publications

None provided.

• Responsible Party: Seema Mital, Principal Investigator, The Hospital for Sick Children
• ClinicalTrials.gov Identifier: NCT04036799
• Other Study ID Numbers: 1000055819
• First Posted: Jul 30, 2019
• Last Update Posted: May 24, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Seema Mital, Principal Investigator, The Hospital for Sick Children: Pediatric; Risk Prediction
• Additional relevant MeSH terms: Cardiomyopathies; Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac; Death; Hypertrophy

Study Results

Participant Flow

Recruitment Details

This was a multicenter retrospective observational cohort study of pediatric patients with clinically diagnosed childhood-onset HCM. The primary cohort included patients from 11 sites participating in the PRIMaCY study (Precision Medicine for Cardiomyopathy), an international registry of patients with pediatric HCM launched in 2017. These included 4 Canadian, 6 US, and 1 Australian site. For model validation, we used data from the Sarcomeric Human Cardiomyopathy Registry.

Arm/Group Title	Hypertrophic Cardiomyopathy
Arm/Group Description	Patients with a clinical diagnosis of HCM defined as having an LV posterior wall or septal thickness z score ≥2.
Period Title: Overall Study
STARTED	572
COMPLETED	572
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Hypertrophic Cardiomyopathy
Arm/Group Description	Patients included were those with a clinical diagnosis of HCM defined as having LV posterior wall or septal thickness z score ≥2, age <18 years at the time of diagnosis, absence of a SCD event before diagnosis, and at least 1 follow-up assessment after diagnosis.
Overall Participants	572
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	9.8
Sex: Female, Male (Count of Participants)
Female	178 31.1%
Male	394 68.9%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	235 41.1%
Canada	273 47.7%
Australia	64 11.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With a Composite Sudden Cardiac Death Event
Description	The composite SCD event includes post diagnosis SCD, aborted SCD (including ventricular fibrillation, sustained ventricular tachycardia), primary ICD insertion with appropriate shock, secondary ICD insertion
Time Frame	Time to a composite sudden cardiac death event during 5-year follow-up

Outcome Measure Data

Analysis Population Description

Patients with a clinical diagnosis of HCM defined as having an LV posterior wall or septal thickness z score ≥2, age <18 years at the time of diagnosis, absence of a sudden cardiac death event before diagnosis, and at least 1 follow-up assessment after diagnosis.

Arm/Group Title	Hypertrophic Cardiomyopathy
Arm/Group Description	Phenotype-positive HCM diagnosed between 1987 and 2018
Measure Participants	572
Count of Participants [Participants]	53 9.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Hypertrophic Cardiomyopathy
	Comments
	Type of Statistical Test	Other
	Comments	Categorical variables were summarized using frequencies and proportions.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Cumulative proportion of events at 5 yrs
	Estimated Value	9.1
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Adverse Event Reporting Description	Adverse events were not captured as this was a retrospective observational cohort study
Arm/Group Title	Hypertrophic Cardiomyopathy
Arm/Group Description	Patients with a clinical diagnosis of HCM defined as having an LV posterior wall or septal thickness z score ≥2.
All Cause Mortality
	Hypertrophic Cardiomyopathy
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Serious Adverse Events
	Hypertrophic Cardiomyopathy
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Hypertrophic Cardiomyopathy
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

The study has limitations inherent to any retrospective analysis, that includes missing data, survivor bias, and lower uptake of genetic testing in the earlier era. Missing echocardiographic data were addressed through a re-review of echocardiograms where available and through imputation where this was not possible. We deliberately did not perform an echocardiographic core laboratory analysis because a real-world, point-of-care tool has to rely on locally acquired data.

More Information

Certain Agreements

Principal Investigators are NOT 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.