Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03398954
Other study ID # 20177276
Secondary ID
Status Recruiting
Phase N/A
First received December 20, 2017
Last updated March 8, 2018
Start date January 18, 2018
Est. completion date December 30, 2019

Study information

Verified date January 2018
Source China Cardiovascular Association
Contact huo yong, master
Phone 13901333060
Email drhuoyong@163.com
Is FDA regulated No
Health authority
Study type Observational [Patient Registry]

Clinical Trial Summary

1. Primary Objective To estimate the prevalence of clinical diagnosed familial hypercholesterolemia, as well as the clinical characteristics and current treatment, with applying China recent issued FH screening protocol in pilot outpatient department of China.

2. Study Design The study is a prospective observational research study of clinical diagnoses FH patients in outpatient department in pilot hospitals to evaluate the screening out rate and the clinical feature and management of FH patients including HoFH, with applying China recent issued FH screening protocol.

3. Eligibility 3.1.Inclusion Criteria Written inform consent provided. Male and female cardiovascular outpatients and inpatients with LDL-C>4.65mmol/L if statin naïve or LDL-C>3.7mmol/L if on statin treatment before enrollment during Sept.2017 to Sept. 2019.

3.2Exclusion Criteria Subjects who cannot understand study procedure Subjects diagnosed as secondary dyslipidemia

4. Primary Endpoint

- The screening out rate of clinical diagnosed familial hypercholesterolemia, with applying China recent issued FH screening protocol in subjects with LDL-C>4.65mmol/L if statin naïve or LDL-C>3.7mmol/L if on statin treatment in pilot outpatient department of China.

- The clinical characteristics of clinical diagnosed FH patients(including HoFH and HeFH), including: demography, medical history, family history, sign and symptoms, lab testing and cardiovascular imagine result.

- The pharmaceutical therapy for clinical diagnosed FH patients (including HoFH and HeFH), including the type of medication, proportion for each medication, dosage and treatment duration.


Description:

1. Objective 1.1.Primary Objective To estimate the prevalence of clinical diagnosed familial hypercholesterolemia, as well as the clinical characteristics and current treatment, with applying China recent issued FH screening protocol in pilot outpatient department of China.

1.2.Secondary Objective To describe parameters related to clinical management of diagnosed FH, including patient demographics and characteristics, LDL-C and triglyceride concentrations, use of lipid modifying therapies, and outcomes over time.

1.3.Exploratory To describe how China FH screening protocol fits in the practice when compared with DLCN.

To explore the multi-disciplinary practical pattern of FH patient management

2. Endpoint(s)/Outcome(s) Assessment 2.1.Endpoint(s) 2.1.1.Primary Endpoint The screening out rate of clinical diagnosed familial hypercholesterolemia, with applying China recent issued FH screening protocol in subjects with LDL-C>4.65mmol/L if statin naïve or LDL-C>3.7mmol/L if on statin treatment in pilot outpatient department of China.

The clinical characteristics of clinical diagnosed FH patients(including HoFH and HeFH), including: demography, medical history, family history, sign and symptoms, lab testing and cardiovascular imagine result.

The pharmaceutical therapy for clinical diagnosed FH patients (including HoFH and HeFH), including the type of medication, proportion for each medication, dosage and treatment duration.

2.1.2.Secondary Endpoint LDL-C level during the follow up period The pharmaceutical therapy for clinical diagnosed FH patients (including HoFH and HeFH), including the type of medication, proportion for each medication, dosage and treatment duration during the follow up period.

Achievement of 2016 China guideline defined target LDL-C levels; <2.6mmol/L (high risk), <1.8mmol/L (very high risk) Incidence of cardiovascular event (CV death, all-cause mortality, non-fatal MI, non-fatal stroke).

2.1.3Exploratory Endpoint The difference of FH screening out rate between China criteria and DLCN. 2.2.Study Parameters 2.2.1.Baseline Data Collection Demography data:Age,Gender, Personal history:Premature CHD history of the subject (male: <55yrs, female: <65yrs),Premature PAD or cerebral vascular disease of the subject (male: <55yrs, female: <65yrs),Smoking, Medical history:PAD,DM,Hypertension,Heart Failure,Stroke,MI,CABG/PTCA/PCI,CKD Family history:Premature CHD within 2nd grade relatives (1st grade relatives, male: <55yrs, female: <60yrs; 2nd grade relatives, male: <50yrs, female: <55yrs),FH diagnosis within 2nd grade relatives Physical exam:Height,Weight,BMI,Corneal Arcus,Xanthoma,Achilles tender thickness Lab:LDL-C,HDL-C ,TC,TG,Lp(a),ALT,AST,CK,Glucose,Creatinine,Urea nitrogen,Inflammatory biomarker, including hs CRP ECG Cardiovascular imagine:CAG(optional),Myocardial radionuclide imaging (optional),UCG(annually),Carotid plaques measure(annually) Lipid modification therapy:Statin(type, dosage),Non-Statin(type, dosage) Apheresis 2.2.2Study Follow Up Period Data Collection Lab:LDL-C,HDL-C,TC,TG,Lp(a),ALT,AST,CK,Glucose,Creatinine,Urea nitrogen Inflammatory biomarker, including hs CRP Cardiovascular imagine:CAG(optional),Myocardial radionuclide imaging (optional),UCG(annually),Carotid plaques(annually) Lipid modification therapy:Statin(type, dosage),Non-Statin(type, dosage) Apheresis; Achievement of 2016 China guideline defined target LDL-C levels; <2.6mmol/L (high risk), <1.8mmol/L (very high risk); Incidence of cardiovascular event (CV death, all-cause mortality, non-fatal MI, non-fatal stroke).

3. STATISTICAL ANALYSIS 3.1.Statistical Inference No formal hypothesis will be tested in this study. This study will estimate the prevalence of Familial Hypercholesterolemia and the related 95% confidence interval in the China outpatient population in pilot hospitals.

3.2.Sample Size Considerations Based on initial feasibility analyses,revealed an approximate annual patient population in cardiology outpatients is 1,000pts/month(50pts/day*20days) with lipid profile measured to be screened. It is estimated that about 3000 patients out of cardiology department will measure their lipid profile in the clinical laboratory, the working days for the outpatient department is defined as 10mon, then total patients number in the outpatient will be about 4000pts/mon/center*10mon=40,000/center/yr. The prevalence of suspected patients based on LDL-C level is 0.47%, then 188 clinical diagnosed patients/center/year to be transited to the follow up period. Based on the planned site number of 6, total patient to be enrolled to this study will be 1128. Based on the prevalence of HoFH is near 1/160,000~1/300,000, it is estimated that 1~2 HoFH patients will be identified from this patient population.

3.3.Planned Analyses All summaries of the data will be descriptive in nature. For categorical variables (including the primary outcome measure), the frequency and percentage, with 95% confidence interval, will be given. Summary statistics for continuous variables will include the number of subjects, mean, median, standard deviation or standard error, 25th percentile (Q1), 75th percentile (Q3), minimum, and maximum. The outcomes over time data will be evaluated using time to event analyses/Cox proportional hazards models. All planned analyses will be descriptive. SAS version 9.2 (or a newer version) will be used for all Data Management and Statistical Analyses.

3.3.1.Description of Study Enrollment All subjects enrolled into the study who meet the inclusion criteria will be included in the full analysis set and will be included in all summaries and analyses.

3.3.2.Description of Subject/Patient Characteristics Clinical characteristics of subjects in the study will be summarized. Measurements such as age will be based on the status at the start of the observation period for the subject, and clinical characteristics such as CV events will be captured throughout the 3.3.3.Primary Analysis Primary Objective

-To estimate the screen out rate of clinical diagnosed familial hypercholesterolemia in outpatient department of China.

Prevalence: Prevalence of suspected FH will be estimated using the patients' data who visited the outpatients department in pilot hospitals and with measurable LDL-C data and validated by China criteria and DNCL respectively. Prevalence will be reported annually for the years 2017-2019.

-To describe parameters related to clinical management of diagnosed FH, including patient demographics and characteristics, LDL-C and triglyceride concentrations, use of lipid modifying therapies, and outcomes over time.

Patient demographics: Analyses of prevalence will be estimated for the following demographic characteristics: age, gender, and region.

Patient clinical characteristics: The proportion of patients, calculated as percentage of patients, for each of the following: BMI (obese/not obese), diabetes, CKD, hypertension, any CVD history / number of CV events, smoking status (current / previous). These will be measured both at baseline (time of FH diagnosis).

Current use of lipid-modifying therapies over time: Proportion of patients using LMT. Analyses by type, dose and frequency will analysis with description statistical method.

Secondary Objective

- LDL-C concentrations over time. The LDL-C level will be follow up to the end of study.

- Use of lipid-modifying therapies over time。 Proportion of patients using LMT. Analyses by type, dose and frequency, and the proportion of patients on a high-intensity statin regime and with high LDL-C will be performed.

- Proportion of patients within and at distance from 2016 China guideline's LDL-C target.

This will be calculated as the percentage of patients within 2016 China guideline LDL-C target (<2.6 mmol/L, <1.8 mmol/L). LDL-C measurements will be followed up to the end of study.

-Incidence of fatal and non-fatal cardiovascular events The proportion of patients having a fatal or non-fatal cardiovascular event will be calculated. Since there may be competing risks with fatal / non-fatal events, analyses will be performed separately, and in combination. All events occurring from date of enrollment of the study onwards will be included.

3.3.4.General Considerations The first primary objective and all secondary objectives will be addressed through descriptive statistics. The CV outcome will be evaluated using time to event analyses.

3.3.5.Missing or Incomplete Data and Lost to Follow-up There are two types of data in this study. For different data types, we will apply different methods to handle missing data.

For Medical records abstraction:

The missing age values will be imputed as the overall median to avoid case-wise deletions. For some of the patients, certain physiological indicators were not measured during hospitalization. These variables will be treated as a specific "unmeasured" subgroup with clinical significance because not measured is not equal to "missing" and may influence the outcomes. If we fit these variables as continuous in the models, we could only arbitrarily consider these "unmeasured" as missing value as inappropriate. Imputation also has limitations. Thus, to keep the models consistent with the features of data, we will transform certain continuous variables into categorical ones, created dummy variables accordingly, and including a specific category to indicate unmeasured.

For Baseline and follow-up questionnaires:

Site investigators completed the questionnaires in an electronic data capture program on a tablet computer (which allows real-time logic checks to ensure the accuracy and completeness of data). All questions were required to be answered, except those that were not applicable. There were options of "refuse to answer" and "don't know" for each question.

4. SAFETY DATA COLLECTION, RECORDING, AND REPORTING Due to the non-interventional nature of this study, no pro-active safety data collection will take place. Only spontaneously mentioned safety events and in-hospital clinical events will be collected in this study, and reported follow by local regulation.


Recruitment information / eligibility

Status Recruiting
Enrollment 1128
Est. completion date December 30, 2019
Est. primary completion date December 30, 2019
Accepts healthy volunteers No
Gender All
Age group N/A and older
Eligibility Inclusion Criteria:

- Written inform consent provided.

- Male and female cardiovascular outpatients and inpatients with LDL-C>4.65mmol/L if statin naïve or LDL-C>3.7mmol/L if on statin treatment before enrollment during Sept.2017 to Sept. 2019.

Exclusion Criteria:

- Subjects who cannot understand study procedure

- Subjects diagnosed as secondary dyslipidemia

Study Design


Locations

Country Name City State
China Beijing Anzhen Hospital Beijing Beijing

Sponsors (2)

Lead Sponsor Collaborator
China Cardiovascular Association Amgen

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary The screening out rate of FH The screening out rate of clinical diagnosed familial hypercholesterolemia, with applying China recent issued FH screening protocol in subjects with LDL-C>4.65mmol/L if statin naïve or LDL-C>3.7mmol/L if on statin treatment in pilot outpatient department of China. 2 years
Primary The clinical characteristics of clinical diagnosed FH patients The clinical characteristics of clinical diagnosed FH patients(including HoFH and HeFH), including: demography, medical history, family history, sign and symptoms, lab testing and cardiovascular imagine result 2 years
Primary The pharmaceutical therapy for clinical diagnosed FH patients The pharmaceutical therapy for clinical diagnosed FH patients (including HoFH and HeFH), including the type of medication, proportion for each medication, dosage and treatment duration 2 years
Secondary LDL-C concentrations over time LDL-C level during the follow up period 2 years
Secondary Use of lipid-modifying therapies over time The pharmaceutical therapy for clinical diagnosed FH patients (including HoFH and HeFH), including the type of medication, proportion for each medication, dosage and treatment duration during the follow up period 2 years
Secondary Proportion of patients within and at distance from 2016 China guideline's LDL-C target Achievement of 2016 China guideline defined target LDL-C levels; <2.6mmol/L (high risk), <1.8mmol/L (very high risk) 2 years
Secondary Incidence of cardiovascular event Incidence of cardiovascular event (CV death, all-cause mortality, non-fatal MI, non-fatal stroke) 2 years
See also
  Status Clinical Trial Phase
Enrolling by invitation NCT05284513 - Collaborative Approach to Reach Everyone With Familial Hypercholesterolemia (CARE-FH) N/A
Enrolling by invitation NCT05271305 - Pilot Study for a National Screening for Familial Hypercholesterolemia
Completed NCT02750527 - Pediatric Population Screening for Type 1 Diabetes and Familial Hypercholesterolemia in Lower Saxony, Germany
Not yet recruiting NCT00924339 - Soy Food Intervention Trial N/A
Withdrawn NCT00751608 - Effect of APL180 on Endothelial Function in Familial Hypercholesterolemia Patients Phase 2
Terminated NCT00079846 - Implitapide in Patients With Homozygous Familial Hypercholesterolemia (HoFH) on Maximal Concurrent Lipid-Lowering Therapy Phase 2
Completed NCT02624869 - Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia) Phase 3
Recruiting NCT05758779 - The Danish Familial Hypercholesterolemia Organized Coronary Screening Trial N/A
Enrolling by invitation NCT04929457 - Evaluation of a Digiphysical Screening Method to Identify and Diagnose Familial Hypercholesterolemia
Not yet recruiting NCT04455581 - A Study to Determine the Safety, Tolerability, and Efficacy of SHR-1209 in Patients With Familial Hypercholesterolemia Phase 2
Recruiting NCT04101149 - Genetic Causes of Familial Hypercholesterolemia
Completed NCT00943306 - Long Term, Follow-on Study of Lomitapide in Patients With Homozygous Familial Hypercholesterolemia Phase 3
Completed NCT02462655 - Effects of LDL Apheresis System on the Expression of Genes Involved in Lipoprotein Metabolism and Inflammation in Homozygotes for Familial Hypercholesterolemia N/A
Terminated NCT00079859 - Implitapide in Patients With Heterozygous Familial Hypercholesterolemia (HeFH) on Maximal Concurrent Lipid-Lowering Therapy Phase 2
Recruiting NCT05066932 - Advanced Lipoproptein Profiling and Cardiovascular Risk Stratification in Familial Hypercholesterolemia
Not yet recruiting NCT04958629 - A Prospective Cohort Study on Familial Hypercholesterolemia in Health Examination Population
Completed NCT02709850 - Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS ANGPTL3-LRx in Healthy Volunteers With Elevated Triglycerides and Participants With Familial Hypercholesterolemia Phase 1
Active, not recruiting NCT03832985 - Pediatric Reporting of Adult-Onset Genomic Results Early Phase 1
Terminated NCT02013713 - French Observatory of Familial Hypercholesterolemia in Cardiology
Recruiting NCT02009345 - Familial Hypercholesterolemia Canada / Hypercholesterolemie Familiale Canada