NCT06129331

Brief Summary

The dual pathology of aortic stenosis (AS) and cardiac amyloidosis (CA) is increasingly recognized. Even tough efforts have been undertaken to bring cohorts together, the largest cohort of AS-ATTR to date is \<50 patients. It is the aim of the present international, multi-center registry to collect \~300 patients with AS-CA creating a big enough cohort to allow

  1. 1.thorough characterization of this condition
  2. 2.assessment of log-term clinical outcomes of AS-CA
  3. 3.assessment of effectiveness of amyloid-specific treatment on top of valve replacement

Trial Health

47
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
300

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Mar 2023

Geographic Reach
2 countries

2 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2023

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

November 2, 2023

Completed
11 days until next milestone

First Posted

Study publicly available on registry

November 13, 2023

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2024

Completed
Last Updated

November 13, 2023

Status Verified

November 1, 2023

Enrollment Period

1.8 years

First QC Date

November 2, 2023

Last Update Submit

November 8, 2023

Conditions

Cardiac AmyloidosisAortic Stenosis

Outcome Measures

Primary Outcomes (4)

  • Phenotyping of AS with "early" ATTR infiltration (DPD grade 1) versus "advanced" ATTR cardiomyopathy (DPD grade 2/3)

    Dual pathology patients with DPD grade 1 will be compared to those with DPD grade 2/3 with regards to symptoms (New York Heart Association functional class), functional capacity (6-Minute walk distance), biomarkers (NT-proBNP and high-sensitive Troponin), and imaging markers on transthoracic echocardiography (e.g., left ventricular ejection fraction, global longitudinal strain, stroke volume index, left ventricular mass). Differences between groups for all of these variables will be analyzed with the Wilcoxon rank sum test.

    0 months

  • All cause mortality in AS-CA with versus without CA-specific treatment

    All-cause mortality analyzed by Cox regression analysis and Kaplan Meier estimates in AS-CA with versus without CA-specific treatment

    60 months

  • Hospitalization for heart failure in AS-CA with versus without CA-specific treatment

    Hospitalization for heart failure analyzed by Cox regression analysis and Kaplan Meier estimates in AS-CA with versus without CA-specific treatment

    60 months

  • Cardiovascular mortality in AS-CA with versus without CA-specific treatment

    Cardiovascular mortality analyzed by Cox regression analysis and Kaplan Meier estimates in AS-CA with versus without CA-specific treatment

    60 months

Secondary Outcomes (3)

  • Natural history of AS-ATTR after valve replacement

    60 months

  • Composite of hospitalization for heart failure and/or death in AS-CA with versus without CA-specific treatment

    60 months

  • Heart failure hospitalzation rate in AS-CA with versus without CA-specific treatment

    36 months

Study Arms (2)

AS-CA without amyloid-specific treatment

Patients with no amyloid-specific treatment

Other: No amyloid-specific treatment

AS-CA with amyloid-specific treatment

Patients receiving newly available amyloid-specific drugs

Drug: Amyloid-specific treatment

Interventions

Amyloid-specific treatmentDRUG

Amyloid-specific treatment

AS-CA with amyloid-specific treatment
No amyloid-specific treatmentOTHER

No amyloid-specific treatment

AS-CA without amyloid-specific treatment

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Patients with a dual pathology of significant aortic stenosis and concomitant cardiac amyloidosis

You may not qualify if:

  • Patients without significant AS (less than moderate AS)
  • Patients with other subtypes of cardiac amyloidosis (e.g., light chain)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Medical University of Vienna

Vienna, 1090, Austria

RECRUITING

University College London

London, United Kingdom

RECRUITING

Related Publications (8)

  • Nitsche C, Scully PR, Patel KP, Kammerlander AA, Koschutnik M, Dona C, Wollenweber T, Ahmed N, Thornton GD, Kelion AD, Sabharwal N, Newton JD, Ozkor M, Kennon S, Mullen M, Lloyd G, Fontana M, Hawkins PN, Pugliese F, Menezes LJ, Moon JC, Mascherbauer J, Treibel TA. Prevalence and Outcomes of Concomitant Aortic Stenosis and Cardiac Amyloidosis. J Am Coll Cardiol. 2021 Jan 19;77(2):128-139. doi: 10.1016/j.jacc.2020.11.006. Epub 2020 Nov 9.

    PMID: 33181246RESULT

  • Nitsche C, Aschauer S, Kammerlander AA, Schneider M, Poschner T, Duca F, Binder C, Koschutnik M, Stiftinger J, Goliasch G, Siller-Matula J, Winter MP, Anvari-Pirsch A, Andreas M, Geppert A, Beitzke D, Loewe C, Hacker M, Agis H, Kain R, Lang I, Bonderman D, Hengstenberg C, Mascherbauer J. Light-chain and transthyretin cardiac amyloidosis in severe aortic stenosis: prevalence, screening possibilities, and outcome. Eur J Heart Fail. 2020 Oct;22(10):1852-1862. doi: 10.1002/ejhf.1756. Epub 2020 Feb 20.

    PMID: 32078212RESULT

  • Nitsche C, Koschutnik M, Dona C, Radun R, Mascherbauer K, Kammerlander A, Heitzinger G, Dannenberg V, Spinka G, Halavina K, Winter MP, Calabretta R, Hacker M, Agis H, Rosenhek R, Bartko P, Hengstenberg C, Treibel T, Mascherbauer J, Goliasch G. Reverse Remodeling Following Valve Replacement in Coexisting Aortic Stenosis and Transthyretin Cardiac Amyloidosis. Circ Cardiovasc Imaging. 2022 Jul;15(7):e014115. doi: 10.1161/CIRCIMAGING.122.014115. Epub 2022 Jul 8.

    PMID: 35861981RESULT

  • Patel KP, Scully PR, Nitsche C, Kammerlander AA, Joy G, Thornton G, Hughes R, Williams S, Tillin T, Captur G, Chacko L, Kelion A, Sabharwal N, Newton JD, Kennon S, Ozkor M, Mullen M, Hawkins PN, Gillmore JD, Menezes L, Pugliese F, Hughes AD, Fontana M, Lloyd G, Treibel TA, Mascherbauer J, Moon JC. Impact of afterload and infiltration on coexisting aortic stenosis and transthyretin amyloidosis. Heart. 2022 Jan;108(1):67-72. doi: 10.1136/heartjnl-2021-319922. Epub 2021 Sep 8.

    PMID: 34497140RESULT

  • Scully PR, Patel KP, Saberwal B, Klotz E, Augusto JB, Thornton GD, Hughes RK, Manisty C, Lloyd G, Newton JD, Sabharwal N, Kelion A, Kennon S, Ozkor M, Mullen M, Hartman N, Cavalcante JL, Menezes LJ, Hawkins PN, Treibel TA, Moon JC, Pugliese F. Identifying Cardiac Amyloid in Aortic Stenosis: ECV Quantification by CT in TAVR Patients. JACC Cardiovasc Imaging. 2020 Oct;13(10):2177-2189. doi: 10.1016/j.jcmg.2020.05.029. Epub 2020 Aug 5.

    PMID: 32771574RESULT

  • Scully PR, Patel KP, Treibel TA, Thornton GD, Hughes RK, Chadalavada S, Katsoulis M, Hartman N, Fontana M, Pugliese F, Sabharwal N, Newton JD, Kelion A, Ozkor M, Kennon S, Mullen M, Lloyd G, Menezes LJ, Hawkins PN, Moon JC. Prevalence and outcome of dual aortic stenosis and cardiac amyloid pathology in patients referred for transcatheter aortic valve implantation. Eur Heart J. 2020 Aug 1;41(29):2759-2767. doi: 10.1093/eurheartj/ehaa170.

    PMID: 32267922RESULT

  • Treibel TA, Fontana M, Gilbertson JA, Castelletti S, White SK, Scully PR, Roberts N, Hutt DF, Rowczenio DM, Whelan CJ, Ashworth MA, Gillmore JD, Hawkins PN, Moon JC. Occult Transthyretin Cardiac Amyloid in Severe Calcific Aortic Stenosis: Prevalence and Prognosis in Patients Undergoing Surgical Aortic Valve Replacement. Circ Cardiovasc Imaging. 2016 Aug;9(8):e005066. doi: 10.1161/CIRCIMAGING.116.005066.

    PMID: 27511979RESULT

  • Nitsche C, Dobner S, Rosenblum HR, Patel KP, Longhi S, Yilmaz A, Merlo M, Papathanasiou M, Griffin J, Oerlemans MIFJ, Gama F, Hamdan A, Kelion AD, Schuster A, Glaveckaite S, Akyol N, Porcari A, Schlender L, Capovilla T, Autherith M, Hauptmann L, Halavina K, Cavalcante JL, Fontana M, Scully PR, Moon JC, Mascherbauer J, Ristl R, Biagini E, Stortecky S, Maurer MS, Treibel TA; AS-Amyloidosis Consortium. Cardiac transthyretin amyloidosis treatment improves outcomes after aortic valve replacement for severe stenosis. Eur Heart J. 2025 Nov 21;46(44):4795-4806. doi: 10.1093/eurheartj/ehaf362.

    PMID: 40452225DERIVED

MeSH Terms

Conditions

Amyloid Neuropathies, FamilialAortic Valve Stenosis

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesNervous System DiseasesAmyloid NeuropathiesPeripheral Nervous System DiseasesNeuromuscular DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesAmyloidosis, FamilialMetabolism, Inborn ErrorsMetabolic DiseasesNutritional and Metabolic DiseasesAmyloidosisProteostasis DeficienciesAortic Valve DiseaseHeart Valve DiseasesHeart DiseasesCardiovascular DiseasesVentricular Outflow Obstruction

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principle Investigator

Study Record Dates

First Submitted

November 2, 2023

First Posted

November 13, 2023

Study Start

March 1, 2023

Primary Completion

December 31, 2024

Study Completion

December 31, 2024

Last Updated

November 13, 2023

Record last verified: 2023-11

Data Sharing

IPD Sharing
Will not share

Locations

AU(1)GB(1)