Clinical trial NCT04507984: Universal Familial Hypercholesterolemia Screening in Children
Official title: Universal Screening for Familial Hypercholesterolemia in Children - a Practical Approach
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Familial Hypercholesterolemia
Polygenic Hypercholesterolaemia
Keywords: familial hypercholesterolemia
FH
screening
universal
cascade
pediatric
Lead sponsor: University of Ljubljana, Faculty of Medicine
Sponsor class: OTHER
Collaborators: name: University Medical Centre Ljubljana
name: Kinderkrankenhaus auf der Bult
First posted: 2020-08-11
Enrollment: 17000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Slovenian cohort: A three-step approach of universal hypercholesterolemia screening is implemented: (1) total cholesterol (TC) measurement in all children at their primary care pediatricians at the programed visit prior to school entry; (2) if above the cut-off, re-testing and/or referral to the lipid clinic, where fasting LDL-cholesterol (LDL-C) measurement is performed; if again above the cut-off, it is followed by FH genetic testing; (3) if FH confirmed, screening of parent with higher TC/LDL-C level.

Lower Saxony cohort: (1) LDL-C measurement was offered to all children between 2-6 years during the compulsory routine check-ups and at any voluntary visits to the pediatrician's office; (2) if twice above the cut-off, referral to the lipid clinic, followed by FH genetic testing.

Brief summary: 30 million individuals globally with undiagnosed familial hypercholesterolemia (FH) are at a substantial cardiovascular disease (CVD) risk, which could be normalized by early diagnosis and treatment. Effective screening strategies are urgently needed, but the data on universal FH screening (uFHs) is scarce.

The investigators aim to assess the overall performance of the uFHs program in Slovenia and to compare the common elements to the pilot uFHs program in Lower Saxony (LS; Germany).

Detailed description: The study will include pediatric patients (or their siblings and parents in Slovenian cohort) undergoing the universal hypercholesterolemia screening; those with elevated cholesterol at universal cholesterol screening at primary care level are referred to the lipidology specialist at the UMC Ljubljana (Slovenia) or Kinderkrankenhaus auf der Bult (Lower Saxony, Germany). For those with elevated cholesterol levels, the familial hypercholesterolemia genetic diagnostics is done centrally in UMC Ljubljana.

Only those will be included from whom a signed informed consent by themselves or by their parents/guardians will be obtained prior to the genetic diagnosis of familial hypercholesterolemia.

Eligibility criteria: Inclusion Criteria:

* Elevated total cholesterol (cohort 1) or LDL-cholesterol (cohort 2) at universal screening program in children.
* Completed FH genetic analysis (cohort 3).
* Parent or sibling of child with confirmed familial hypercholesterolemia (cohort 4).

Exclusion Criteria:

* Children with hypercholesterolemia not referred through the screening program.
* FH genetic analysis not completed.

Primary outcomes:
measure: Efficacy of universal familial hypercholesterolemia screening
timeFrame: 36 months
Secondary outcomes:
measure: Genotype-phenotype correlations in children with familial hypercholesterolemia
timeFrame: 36 months
measure: Prevalences of heterozygous and homozygous familial hypercholesterolemia
timeFrame: 36 months
measure: Cost-effectiveness analysis of universal screening for familial hypercholesterolemia
timeFrame: 36 months
measure: Comparison of universal and pilot familial hypercholesterolemia screening
timeFrame: 36 months
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Children's Hospital AUF DER BULT
city: Ljubljana
country: Slovenia
facility: UMC - University Children's Hospital Ljubljana
Study officials:
affiliation: University of Ljubljana, Faculty of Medicine
name: Urh Groselj, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kinderkrankenhaus auf der Bult
name: Olga Kordonouri, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, Wiklund O, Hegele RA, Raal FJ, Defesche JC, Wiegman A, Santos RD, Watts GF, Parhofer KG, Hovingh GK, Kovanen PT, Boileau C, Averna M, Boren J, Bruckert E, Catapano AL, Kuivenhoven JA, Pajukanta P, Ray K, Stalenhoef AF, Stroes E, Taskinen MR, Tybjaerg-Hansen A; European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013 Dec;34(45):3478-90a. doi: 10.1093/eurheartj/eht273. Epub 2013 Aug 15.
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citation: Representatives of the Global Familial Hypercholesterolemia Community; Wilemon KA, Patel J, Aguilar-Salinas C, Ahmed CD, Alkhnifsawi M, Almahmeed W, Alonso R, Al-Rasadi K, Badimon L, Bernal LM, Bogsrud MP, Braun LT, Brunham L, Catapano AL, Cillikova K, Corral P, Cuevas R, Defesche JC, Descamps OS, de Ferranti S, Eisele JL, Elikir G, Folco E, Freiberger T, Fuggetta F, Gaspar IM, Gesztes AG, Groselj U, Hamilton-Craig I, Hanauer-Mader G, Harada-Shiba M, Hastings G, Hovingh GK, Izar MC, Jamison A, Karlsson GN, Kayikcioglu M, Koob S, Koseki M, Lane S, Lima-Martinez MM, Lopez G, Martinez TL, Marais D, Marion L, Mata P, Maurina I, Maxwell D, Mehta R, Mensah GA, Miserez AR, Neely D, Nicholls SJ, Nohara A, Nordestgaard BG, Ose L, Pallidis A, Pang J, Payne J, Peterson AL, Popescu MP, Puri R, Ray KK, Reda A, Sampietro T, Santos RD, Schalkers I, Schreier L, Shapiro MD, Sijbrands E, Soffer D, Stefanutti C, Stoll M, Sy RG, Tamayo ML, Tilney MK, Tokgozoglu L, Tomlinson B, Vallejo-Vaz AJ, Vazquez-Cardenas A, de Luca PV, Wald DS, Watts GF, Wenger NK, Wolf M, Wood D, Zegerius A, Gaziano TA, Gidding SS. Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia: A Global Call to Action. JAMA Cardiol. 2020 Feb 1;5(2):217-229. doi: 10.1001/jamacardio.2019.5173.
citation: Klancar G, Groselj U, Kovac J, Bratanic N, Bratina N, Trebusak Podkrajsek K, Battelino T. Universal Screening for Familial Hypercholesterolemia in Children. J Am Coll Cardiol. 2015 Sep 15;66(11):1250-1257. doi: 10.1016/j.jacc.2015.07.017.
citation: Groselj U, Kovac J, Sustar U, Mlinaric M, Fras Z, Podkrajsek KT, Battelino T. Universal screening for familial hypercholesterolemia in children: The Slovenian model and literature review. Atherosclerosis. 2018 Oct;277:383-391. doi: 10.1016/j.atherosclerosis.2018.06.858.
citation: Kordonouri O, Lange K, Boettcher I, Christoph J, Marquardt E, Tombois C, Galuschka L, Stiller D, Mueller I, Roloff F, Aschemeier B, Danne T. New approach for detection of LDL-hypercholesterolemia in the pediatric population: The Fr1dolin-Trial in Lower Saxony, Germany. Atherosclerosis. 2019 Jan;280:85-91. doi: 10.1016/j.atherosclerosis.2018.11.011. Epub 2018 Nov 17.