Aortic Stenosis and Cardiac Amyloidosis

Aortic Stenosis Clinical Trial

Official title:

Aortic Stenosis and Cardiac Amyloidosis: A Pragmatic, Streamlined International

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06129331
• Other study ID #: 2218_2016
• Status: Recruiting
• Start date: March 1, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: November 2023
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

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

Description:

Calcific aortic stenosis (AS) and transthyretin (ATTR) cardiac amyloidosis are both conditions commonly affecting the elderly. Bone scintigraphy using amyloid-avid tracers (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, DPD; 99mTc-pyrophosphate; or 99mTc-hydroxymethylene diphosphonate) represents the key imaging modality for non-invasive ATTR diagnosis. Recent studies have used this technology to screen AS patients and demonstrated that AS and ATTR may coexist in 8 to 16%. This is substantially higher than in non-cardiac referrals for bone scintigraphy (range 1-3% in individuals >80 years), which is considered the most accurate approach to estimate the ATTR prevalence in the general population. While the dual burden of AS and ATTR might suggest adverse prognostic implications, it has been shown that AS-ATTR and lone AS patients benefit equally from transcatheter aortic valve replacement (TAVR) with comparable 1- and 2-year survival rates. Yet, data on long-term outcomes are still missing. With increased recognition and valvular treatment of AS-ATTR, the disease course after TAVR becomes a key issue. Our data suggest significantly different remodeling between lone AS and AS-ATTR, with the latter being transformed into a "lone-ATTR" cardiomyopathy phenotype at one-year post-TAVR. Novel ATTR-specific treatments are now available, with the potential to further improve prognosis in AS-ATTR on top of valvular replacement. However, patients with significant AS were not included in the ATTR-ACT trial, and treatment effectiveness in this patient population therefore remains unclear. Also, despite increased ATTR screening globally, the case numbers for dual AS-ATTR of individual centers are still low. The present international multi-center study is therefore designed to provide detailed characterization of dual AS-ATTR, inform about long-term clinical outcomes and assess the effect of ATTR specific treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with significant AS and a concomitant diagnosis of cardiac amyloidosis who are eligible for inclusion as per local permissions

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Amyloidosis
• Aortic Stenosis
• Aortic Valve Stenosis
• Cardiac Amyloidosis
• Constriction, Pathologic

Intervention

Drug:
• Amyloid-specific treatment
Amyloid-specific treatment

Other:
• No amyloid-specific treatment
No amyloid-specific treatment

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna
United Kingdom	University College London	London

Sponsors (11)

Lead Sponsor	Collaborator
Medical University of Vienna	Allina Health System, Columbia University, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Laval University, Medical University of South Carolina, Royal Free Hospital NHS Foundation Trust, Université Catholique de Louvain, University of Trieste, Vilnius University Hospital Santaros Klinikos, Wolfson Medical Center

Countries where clinical trial is conducted

Austria,  United Kingdom, 

References & Publications (7)

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 — View Citation

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 Rem — View Citation

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, Tr — View Citation

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, Ll — View Citation

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 — View Citation

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 — View Citation

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 P — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	Natural history of AS-ATTR after valve replacement	Trajectory of morphological (left ventricular mass), functional (ejection fraction, global longitudinal strain, New York Heart Association class) and biomarker (NT-proBNP, high-sensitive Troponin) profiles. Longitudinal changes between visits will be compared using the Wilcoxon signed-rank test, McNemar's test, and the Stuart Maxwell test where appropriate.	60 months
Secondary	Composite of hospitalization for heart failure and/or death in AS-CA with versus without CA-specific treatment	Composite of hospitalization for heart failure and/or death analyzed by Cox regression analysis and Kaplan Meier estimates in AS-CA with versus without CA-specific treatment	60 months
Secondary	Heart failure hospitalzation rate in AS-CA with versus without CA-specific treatment	Differences in heart failure hospitalization rate, calculated as the number of heart failure hospitalizations per total person-years in AS-CA with versus without CA-specific treatment at 1 and 3 years, analyzed by the poisson model.	36 months