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Study of Awareness and Detection of Familial Hypercholesterolemia (CASCADE-FH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01960244
Recruitment Status : Recruiting
First Posted : October 10, 2013
Last Update Posted : November 6, 2019
Duke Clinical Research Institute
Information provided by (Responsible Party):
The Familial Hypercholesterolemia Foundation

Tracking Information
First Submitted Date September 17, 2013
First Posted Date October 10, 2013
Last Update Posted Date November 6, 2019
Study Start Date October 2013
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: October 8, 2013)
Promote awareness of FH to increase the number of identified FH patients, reaching optimal level of disease management; target treatment levels for LDL cholesterol. [ Time Frame: 3 Years ]
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title Study of Awareness and Detection of Familial Hypercholesterolemia
Official Title CASCADE FH Registry (CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia Registry)
Brief Summary The CASCADE-FH Registry is a national, multi-center initiative that will track the therapy, clinical outcomes, and patient-reported outcomes over time. The registry represents a collaboration between The Familial Hypercholesterolemia Foundation, the Duke Clinical Research Institute, lipid specialists, cardiologists, primary care providers, quality improvement personnel, and patients, all aiming to increase FH awareness, promote optimal disease management, and improve FH outcomes.
Detailed Description

The FH Foundation CASCADE-FH Registry will implement an enrollment framework which is characterized by three possible points of contact: 1) Clinic enrollment 2) Self-enrollment through an online patient portal, and 3) Electronic Health Record (EHR) identification.

Pathway 1: Clinic-Based Screening and Enrollment During the initial study phase, a number of specialized lipid clinics across the US will participate in the CASCADE-FH registry. FH patients at these sites who meet inclusion will enroll. Each site will be required to receive IRB approval and obtain patient consent. Once the initial set of specialized lipid clinics has demonstrated acceptable feasibility for patient enrollment and engagement, additional sites will be recruited into the registry.

Pathway 2: Patient Self-Enrollment Potential registry participants will have the opportunity to self-enroll in the CASCADE-FH Registry through an online screening mechanism. A link on the FH Foundation website ( will direct potential participants to a brief screening questionnaire see inclusion criteria.

Pathway 3: Electronic Health Record (EHR) Screening System-wide searches of EHR to identify potential FH patients based on LDL lab values and clinical FH criteria. Following identification, the primary care provider of the potential FH patient is sent a notification letter describing the patient's high LDL level, at-risk status and need for additional screening. The patient may then undergo additional clinical or genetic testing and be provided information about CASCADE-FH and registry participation.

Data collection For data entered at clinical sites, the primary source of information will be the patient's medical record. Baseline data will elements to be abstracted and entered.

Data elements entered by self-enrolled patients in the online patient portal will include a subset of clinical information as well as questions on quality of life, disease-related anxiety, and depression. A short survey to assess patient understanding of FH health risks, available treatment options, and family member screening will also be included. The patient questionnaire was designed to be free of clinical jargon and pilot-tested by FH patient volunteers to ensure ease of use by participants.

Followup data collection For patients enrolled at clinical sites, providers will be asked to update information at yearly intervals. Medical records will be reviewed to assess changes in medications, occurrence of major adverse cardiovascular events, hospitalizations, genetic testing, and laboratory values updated since the last date of data entry. Follow-up data will be collected yearly for 3 years following initial enrollment. Self-enrolled patients may update data at any time by accessing the patient portal. Updated information on current medication regimens, clinical events, and quality of life will be collected. However, reminder emails will be sent to all self-enrolled patients on an annual basis to ensure uniform entry of follow up information.

Patient-Reported Data Validation To ensure collection of high-quality data on FH patient-reported outcomes, an annual validation of a proportion of self-enrolled patient records will be conducted to assess concordance between information entered in the online patient portal with data from their medical record. Following baseline data entry, self-enrolled patients will be asked to provide contact information for their physicians and to sign a medical release for validation of patient reported data. Of patients signing this medical release, a randomly generated 10% sample will be selected for validation on a yearly basis. Patient responses to questions regarding medication regimens, comorbid conditions, clinical events and lab results will be compared to determine concordance between patient- and physician-reported data. Overall agreement, sensitivity, specificity, and kappa statistics will be evaluated to determine concordance between responses. Based on prior validation analyses of patient-reported data, we expect moderate to good agreement between the two data sources (Κ=0.40-0.80)19,20 Data elements with low rates of concordance will be assessed for clarity and may be refined to enhance sensitivity and specificity. Supplemental educational material may be provided for variables with low concordance to further promote valid data capture.

Longitudinal Outcomes Serial lipid values will be a key outcome of interest and will be examined to assess the adequacy of lipid modifying therapies to achieve target LDL values. Longitudinal outcomes of interest will include medication changes, occurrence of major adverse cardiovascular events, and mortality. Primary patient-reported outcomes of interest will include notification and screening of family members, treatment satisfaction, disease-related perceptions, and quality of life measurements.

Statistical Considerations The CASCADE-FH Registry will collect patient-reported and clinician-reported information to characterize treatment patterns and outcomes among FH patients. Because this study is not-hypothesis driven and no specific medical therapies or treatment interventions are being compared, formal prospective calculations of sample sizes are not necessary. However, we will periodically assess variations in lipid management, clinical events, and patient-reported outcomes to evaluate temporal changes in these variables. Standard statistical approaches commonly used in observational analyses will be utilized.

Data Feedback and Quality Improvement Sites participating in the CASCADE-FH Registry will receive annual data feedback reports that will highlight treatment patterns, serial lipid values, and clinical outcomes for their enrolled patients compared with the national results. These reports will be designed to facilitate quality improvement interventions at participating sites designed to improve the treatment and outcomes of FH patients. Self-enrolled patients will have the opportunity to download their reported data directly as well as through pre-programmed self-feedback, electronic reports that can be accessed at any time.

Study Type Observational [Patient Registry]
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration 3 Years
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Patients diagnosed Familial hypercholesterolemia (FH).
Condition Hypercholesterolemia
Intervention Not Provided
Study Groups/Cohorts hypercholesterolemia
familial hypercholesterolemia
Publications * Duell PB, Gidding SS, Andersen RL, Knickelbine T, Anderson L, Gianos E, Shrader P, Kindt I, O'Brien EC, McCann D, Hemphill LC, Ahmed CD, Martin SS, Larry JA, Ahmad ZS, Kullo IJ, Underberg JA, Guyton J, Thompson P, Wilemon K, Roe MT, Rader DJ, Cuchel M, Linton MF, Shapiro MD, Moriarty PM, Knowles JW. Longitudinal low density lipoprotein cholesterol goal achievement and cardiovascular outcomes among adult patients with familial hypercholesterolemia: The CASCADE FH registry. Atherosclerosis. 2019 Oct;289:85-93. doi: 10.1016/j.atherosclerosis.2019.08.007. Epub 2019 Aug 19.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: October 8, 2013)
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 2025
Estimated Primary Completion Date December 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

Online Patient Enrollment Inclusion Criteria:

  • Patients with existing clinical diagnosis of FH;
  • Patients with genetic mutation of FH;
  • Patients with an initial (pretreatment) LDL level >190 mg/dL or total cholesterol >300 mg/dL;
  • Patients currently taking a lipid-lowering medication and have an LDL >124 mg/dL or total cholesterol >195 mg/dL.

Clinic Patient Enrollment Inclusion Criteria:

  • Patients with existing clinical diagnosis of FH using one of the three clinical diagnostic (US MedPed Program Criteria, Simon Broome Register Criteria with diagnosis of "Probable", Dutch Lipid Clinic Network Diagnostic Criteria with diagnosis of "Probable")tools for FH; or
  • Patients with genetic mutation of FH

Exclusion Criteria:

  • Patients will be excluded from participation in the registry when a known medical condition other than FH that is thought to contribute to hyperlipidemia (i.e., untreated hypothyroidism, nephrotic syndrome, cholestasis hypopituitarism).
Sexes Eligible for Study: All
Ages Child, Adult, Older Adult
Accepts Healthy Volunteers No
Contact: Matthew Brobeck, BS 6265772799
Listed Location Countries United States
Removed Location Countries  
Administrative Information
NCT Number NCT01960244
Other Study ID Numbers Pro00045568
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party The Familial Hypercholesterolemia Foundation
Study Sponsor The Familial Hypercholesterolemia Foundation
Collaborators Duke Clinical Research Institute
Study Director: Katherine Wilemon FHFoundation
PRS Account The Familial Hypercholesterolemia Foundation
Verification Date November 2019