Familial Hypercholesterolemia Interpretive Comment - Nudging to Detection.

NCT05614219 | Recruiting

• 1 other identifier: FINDRSYD22
• Study Type: interventional
• Target: 2,000
• Locations: 1 country
• Sites: 2

Brief Summary

Familial hypercholesterolemia is the most common inherited disease of the lipid metabolism, however it remains underdiagnosed. Only 15 % of 30.000 possible patients have been found in Denmark. This quality assessing project will through a step wedge cluster randomized controlled trial evaluate establishment of a biochemistry interpretive comment on elevated LDL-C levels. The study will test if the comment results in an increase in referred patients to the lipid clinics of Southern Denmark as the primary endpoint, and as the secondary endpoint in more patients diagnosed with familial hypercholesterolemia. The project will run in totally 52 weeks and will in steps initiate the comment from the different laboratories in the Region of Southern Denmark.

Conditions

Familial Hypercholesterolemia

Keywords

Familial Hypercholesterolemia; Biochemistry interpretive comment; Low-density lipoprotein cholesterol levels; Screening

Outcome Measures

Primary Outcomes (2)

• Number of patients reffered to lipid clinic

  Proportion of referred patients to lipid clinics in the region of Southern Denmark after establishment of interpretive comment on LDL-C, compared to proportion before the comment.

  12-18 months

• Diagnosed patients with Familial Hyperchoelsterolemia

  Proportion of patients diagnosed with familial hypercholesterolemia (Dutch clinical lipid score ≥ 6) in the Region of Southern Denmark after establishment of interpretive comment on LDL-C, compared to proportion before the comment.

  During 9-12 months due to waiting time for genetic test

Secondary Outcomes (7)

• Change in LDL-C

  3-6 months

• Familial hypercholesterolemia mutations

  9-12 months due to waiting time for genetic test

• Hba1C

  3 months

• TSH

  3 months

• Triglycerides

  3 months

Study Arms (2)

Biochemistry interpretive comment on LDL-C levels

EXPERIMENTAL

The general practitioners and hospital wards will be allocated in cluster according to their providing lab, and stepwise implement the comment on LDL-C ≥ 4 mmol/L in persons under the age of 40 and ≥ 5 mmol/L in persons ≥ 40 years. Raising awareness on familial hypercholesterolemia an encouraging to referral. Cluster 1. Will from the 01.12.2022 implement comment on LDL-C Cluster 2. Will from the 01.03.2023 implement comment on LDL-C Cluster 3. Will from the 01.06.2023 implement comment on LDL-C Cluster 4.Will from the 01.09.2023 implement comment on LDL-C

Other: Biochemistry interpretive comment on elevated LDL-C levels

Control

NO INTERVENTION

The clusters will act as their own controls, due to the stepwise implementation of the comment. Cluster 2: Will not implement the comment before the 01.03.2023 Cluster 3: Will not implement the comment before the 01.06.2023 Cluster 4: Will not implement the comment before the 01.09.2023

Interventions

Biochemistry interpretive comment on elevated LDL-C levels OTHER

The interpretive comment on LDL-C will encourage for excluding secondary dyslipidemia (measuring Hba1C, TSH and checking current drugs and talk about diet). If secondary dyslipidemia ca be excluded we encourage to referral to lipid clinic. Familial hypercholesterolemia should be suspected if LDL-C ≥ 4 mmol/L in persons under the age of 40, or LDL-C ≥ 5 mmol/L in persons ≥ 40. The biochemistry interpretive comment will thus be released to the referring physician if the blood sample meet the criteria above. We advice that in pregnant women to control elevated LDL-C after childbirth.

Biochemistry interpretive comment on LDL-C levels

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All referred patients to the lipid clinics of Southern Denmark
• LDL-C ≥ 4 mmol/L in persons under the age of 40.
• LDL-C ≥ 5 mmol/L in persons ≥ 40 years.

You may not qualify if:

• Pregnancy and Secondary dyslipidemia
• Dysregulated diabetes. Hba1C \< 48
• Dysregulated hypothyreosis. Elevated TSH.
• Kombined hyperlipidiemia TG \> 4 mmol/L
• Nefrotic syndrome: proteinuria \> 3 g/L and s-albumin \< 30 g/l
• Cholestasis (alcalic fosfatase \> 105 U/L and GGT \> 55 U/L) 14 days prior to LDL-C measuring
• Pharmacological induced hyperlipidimia

Sponsors & Collaborators

• Odense University Hospital: lead

Study Sites (2)

Odense University Hospital

Odense, Funen, 5000, Denmark

RECRUITING

Departement of Cardiology, Odense University Hospital

Odense C, 5000, Denmark

RECRUITING

Related Publications (10)

• Levenson AE, de Ferranti SD. Familial Hypercholesterolemia. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, et al., editors. Endotext. South Dartmouth (MA)2000.

  BACKGROUND

• Bundgaard H SMea. Regionernes klinisk kvalitetsdatabase. Familiær hyperkolesterolæmi databasen. 2020 [Available from: https://www.rkkp.dk/kvalitetsdatabaser/databaser/databasen-for-familiaer-hyperkolesterolaemi/

  BACKGROUND

• Rosso A, Pitini E, D'Andrea E, Massimi A, De Vito C, Marzuillo C, Villari P. The Cost-effectiveness of Genetic Screening for Familial Hypercholesterolemia: a Systematic Review. Ann Ig. 2017 Sep-Oct;29(5):464-480. doi: 10.7416/ai.2017.2178.

  PMID: 28715059 BACKGROUND

• Sturm AC, Knowles JW, Gidding SS, Ahmad ZS, Ahmed CD, Ballantyne CM, Baum SJ, Bourbon M, Carrie A, Cuchel M, de Ferranti SD, Defesche JC, Freiberger T, Hershberger RE, Hovingh GK, Karayan L, Kastelein JJP, Kindt I, Lane SR, Leigh SE, Linton MF, Mata P, Neal WA, Nordestgaard BG, Santos RD, Harada-Shiba M, Sijbrands EJ, Stitziel NO, Yamashita S, Wilemon KA, Ledbetter DH, Rader DJ; Convened by the Familial Hypercholesterolemia Foundation. Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel. J Am Coll Cardiol. 2018 Aug 7;72(6):662-680. doi: 10.1016/j.jacc.2018.05.044.

  PMID: 30071997 BACKGROUND

• Raal FJ, Hovingh GK, Catapano AL. Familial hypercholesterolemia treatments: Guidelines and new therapies. Atherosclerosis. 2018 Oct;277:483-492. doi: 10.1016/j.atherosclerosis.2018.06.859.

  PMID: 30270089 BACKGROUND

• Hedegaard BS. A danish nationwide study og individuals suspected of FH referred from general practice to lipid clinics: Clinical characteristics, plasma lpipoprotein(A) and final diagnosis. Atherosclerosis. 2021.

  BACKGROUND

• Schmidt EB, Hedegaard BS, Retterstol K. Familial hypercholesterolaemia: history, diagnosis, screening, management and challenges. Heart. 2020 Dec;106(24):1940-1946. doi: 10.1136/heartjnl-2019-316276. Epub 2020 Sep 15. No abstract available.

  PMID: 32933999 BACKGROUND

• Schmidt EB, Henriksen FL, Kanstrup HL. Familiær hyperkolesterolæmi holdningspapir Dansk Cardiologisk Selskab2019 [08.04. 2022]. Available from: https://nbv.cardio.dk/media/com_reditem/files/customfield/item/7349/601670e648780b94c9cf26375caef524dcdb2270.pdf

  BACKGROUND

• Barlow IM. Are biochemistry interpretative comments helpful? Results of a general practitioner and nurse practitioner survey. Ann Clin Biochem. 2008 Jan;45(Pt 1):88-90. doi: 10.1258/acb.2007.007134.

  PMID: 18275680 BACKGROUND

• Hemming K, Haines TP, Chilton PJ, Girling AJ, Lilford RJ. The stepped wedge cluster randomised trial: rationale, design, analysis, and reporting. BMJ. 2015 Feb 6;350:h391. doi: 10.1136/bmj.h391. No abstract available.

  PMID: 25662947 BACKGROUND

MeSH Terms

Conditions

Hyperlipoproteinemia Type II

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Finn Lund Henriksen, Ph.d.

  Departement of Cardiology, Odense University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jakob Knold, MD

CONTACT

004541278928; jakobknold@rsyd.dk

Finn Lund Henriksen, Ph.d.

CONTACT

29679722; finn.l.henriksen@rsyd.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: Step wedge cluster randomized controlled trial.

Study Record Dates

• First Submitted: October 27, 2022
• First Posted: November 14, 2022
• Study Start: December 1, 2023
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2)