Clinical trial NCT06932081: Adult Congenital Heart Disease International EValuation of the Effectiveness of SGLT2i Registry
Official title: Adult Congenital Heart Disease International EValuation of the Effectiveness of SGLT2i (ACHIEVE-SGLT2i) Registry
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Adult Congenital Heart Disease
Congenital Heart Disease
Systemic Right Ventricle
Transposition of the Great Arteries
Congenitally Corrected Transposition of the Great Arteries
Fontan
Single Ventricle
Tetralogy of Fallot (TOF)
Keywords: adult congenital heart disease
ACHD
congenital heart disease
CHD
sodium-glucose cotransporter 2 inhibitors
SGLT2i
SGLT2
heart failure
HF
transposition of the great arteries
TGA
systemic right ventricle
sRV
Fontan
single ventricle
tetralogy of fallot
ToF
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2025-04-17
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All adult patients (≥ 18 years) with congenital heart disease who have been treated with an SGLT2i are eligible for inclusion in the registry.

Brief summary: This real-world, international registry aims to evaluate the current experience with sodium-glucose cotransporter 2 inhibitors (SGLT2i) in adult congenital heart disease (ACHD) patients by investigating the prescription patterns, safety, tolerability, and potential beneficial effects on heart failure-related outcomes.

Detailed description: In the adult congenital heart disease (ACHD) population, heart failure currently represents the main cause of morbidity and mortality. The etiology of ACHD-related heart failure is heterogenous, and there is limited evidence for pharmacological treatment options for this population.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel pillar in the treatment of conventional LV heart failure. SGLT2i have been shown to reduce the risk of worsening heart failure and cardiovascular-related death in patients with LV heart failure.

While the exact mechanisms of action are still to be elucidated, SGLT2i seem to address heart failure by targeting several pathways. These include but are not limited to; a decrease in renin-angiotensin and sympathetic nervous system activation, a decrease in pressure overload-induced myocardial fibrosis, reverse cardiac remodeling, and improvement in myocardial energetics.

Given the compelling evidence on the effectiveness of SGLT2i over a broad range of cardiac dysfunction and initial promising reports of its utilization in the field of ACHD, SGLT2i deserve further exploration in the group of ACHD patients.

This real-world, international registry aims to evaluate the current experience with SGLT2i in ACHD patients by investigating the prescription patterns, safety, tolerability, and potential beneficial effects on heart failure-related outcomes.

Project design:

Data of all ACHD patients who were started on an SGLT2i will be collected in a real-world, international registry. Only data resulting from routine clinical care will be collected from the electronic health records at the participating centers, and participants will not undergo any interventions for this project. Data will be collected from 1 year before starting with the SGLT2i to most recent follow-up after starting with the SGLT2i, to evaluate if SGLT2i therapy halts the progression of clinical deterioration in ACHD patients with heart failure and can improve heart failure-related outcomes.

Eligibility criteria: Inclusion Criteria:

* Congenital heart defect.
* Age ≥ 18 years.
* Initiated on treatment with an SGLT2i.

Exclusion Criteria:

- No consent for data collection.

Primary outcomes:
measure: Prescription patterns
timeFrame: Baseline information.
Secondary outcomes:
measure: Side effects [Safety and Tolerability]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: SGLT2i-related complications [Safety and Tolerability]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: SGLT2i discontinuation [Safety and Tolerability]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Mortality [Safety and Tolerability]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Admissions [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Clinical parameters - weight [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Clinical parameters - systolic blood pressure [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Clinical parameters - diastolic blood pressure [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Clinical parameters - heart rate [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Clinical parameters - saturation [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Laboratory parameters - sodium [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Laboratory parameters - potassium [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Laboratory parameters - creatinine [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Laboratory parameters - eGFR [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Laboratory parameters - NT-proBNP [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Laboratory parameters - glucose [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Laboratory parameters - HbA1c [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Transthoracic echocardiography - LV function [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Transthoracic echocardiography - LV GLS [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Transthoracic echocardiography - LV FAC [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Transthoracic echocardiography - RV function [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Transthoracic echocardiography - RV GLS [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Transthoracic echocardiography - RV FAC [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Transthoracic echocardiography - RV S' [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Transthoracic echocardiography - TAPSE [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Exercise parameters - 6MWT [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Exercise parameters - maximum performance [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Exercise parameters - validity [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Exercise parameters - VO2 max [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Exercise parameters - %-predicted VO2 max [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
measure: Concomitant medication changes [Heart Failure-related Efficacy]
timeFrame: From enrollment through study completion, with an average follow-up duration of 1 year.
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital
state: Michigan
city: New York City
country: United States
facility: Mount Sinai Fuster Heart Hospital
state: New York
city: Leiden
country: Netherlands
facility: Leiden University Medical Center (LUMC)
state: Zuid-Holland
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Skopje
country: North Macedonia
facility: Zan Mitrev Clinic
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Glasgow
country: United Kingdom
facility: Golden Jubilee University National Hospital
city: London
country: United Kingdom
facility: Barts Heart Centre
Study officials:
affiliation: Leiden University Medical Center
name: Anastasia D. Egorova, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Neijenhuis RML, MacDonald ST, Zemrak F, Mertens BJA, Dinsdale A, Hunter A, Walker NL, Swan L, Reddy S, Rotmans JI, Jukema JW, Jongbloed MRM, Veldtman GR, Egorova AD. Effect of Sodium-Glucose Cotransporter 2 Inhibitors in Adults With Congenital Heart Disease. J Am Coll Cardiol. 2024 Apr 16;83(15):1403-1414. doi: 10.1016/j.jacc.2024.02.017. Epub 2024 Mar 25.
citation: Neijenhuis RML, Nederend M, Jongbloed MRM, Kies P, Rotmans JI, Vliegen HW, Jukema JW, Egorova AD. The potential of sodium-glucose cotransporter 2 inhibitors for the treatment of systemic right ventricular failure in adults with congenital heart disease. Front Cardiovasc Med. 2023 Jun 26;10:1093201. doi: 10.3389/fcvm.2023.1093201. eCollection 2023.
citation: Egorova AD, Nederend M, Tops LF, Vliegen HW, Jongbloed MRM, Kies P. The first experience with sodium-glucose cotransporter 2 inhibitor for the treatment of systemic right ventricular failure. ESC Heart Fail. 2022 Jun;9(3):2007-2012. doi: 10.1002/ehf2.13871. Epub 2022 Mar 30.