Randomized, Open-label Trial of Inhibitory Effect of Evogliptin on Progression of CAVD

NCT04521452 | Unknown Phase 4 FDA Drug

• 1 other identifier: DIP_CAVD_DM
• Study Type: interventional
• Target: 218
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess an inhibitory effect of Evogliptin on the progression of mild-to-moderate aortic stenosis in patients with T2DM and calcific aortic stenosis.

Conditions

CAVD

Outcome Measures

Primary Outcomes (1)

• Change in aortic valve calcium volume at week 96 from baseline

  96 weeks

Secondary Outcomes (7)

• Change in aortic valve calcium volume at week 48 from baseline

  96 weeks

• Change in aortic valve calcium score at week 48 and week 96 from baseline

  48 weeks, 96 weeks

• Rate of change (%) in aortic valve calcium volume at week 48 and week 96 from baseline

  48 weeks, 96 weeks

• Change in peak aortic-jet velocity at week 48 and week 96 from baseline

  48 weeks, 96 weeks

• Change in aortic peak & mean pressure gradient at week 48 and week 96 from baseline

  48 weeks, 96 weeks

Study Arms (2)

Evogliptin Group

EXPERIMENTAL

evogliptin 5mg daily

Drug: Evogliptin

Non-evogliptin Group

NO INTERVENTION

DM medications except evogliptin and other DPP-4 inhibitors

Interventions

Evogliptin DRUG

Subjects will receive evogliptin 5 mg daily

Evogliptin Group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female aged 19 years or older
• Subjects who were diagnosed with type 2 diabetes mellitus and being treated with oral hypoglycemic drugs
• Subjects whose Doppler echocardiography or Heart CT performed within 8 weeks prior to or during Screening Visit (Visit 1) is satisfying any of the followings:
• Doppler echocardiogrphy (aortic valve calcification and/or hypertrophy with aortic peak velocity≥2.0 m/s); or
• Heart CT (aortic valve calcium score≥300 AU)
• Subjects who decided to take part in this study on his/her own volition after listening to the details of this study

You may not qualify if:

• Subjects with severe aortic valve stenosis (aortic peak velocity\>4.0 m/s, mean pressure gradient \>40 mmHg, or aortic valve area≤0.75 cm2)
• Subjects with left ventricular ejection fraction \< 40%
• Heart failure patients: Subjects with heart failure of NYHA functional class II-IV
• Subjects with an estimated glomerular filtration rate (eGFR) of \<30ml
• Subjects with type 1 diabetes or diabetic ketoacidosis
• Subjects with serious hypersensitivity to DPP-4 inhibitors
• Subjects who have received/are receiving any of the following medication therapies:
• Vitamin K
• Calcium supplement (or osteoporosis medication)
• Subjects whose aortic valve stenosis is not caused by degenerative or bicuspid valve disease (e.g. rheumatic valve disease)
• Subjects who have received or are expected to receive (as of Visit 1) aortic valve surgery during the study.
• Subjects for whom a two-year clinical course investigation is not possible due to malignant tumor or cerebrovascular disease
• Pregnant or lactating women
• Women of childbearing potential who are sexually active and do not agree to use proper contraception during the study
• Proper contraception means physical barrier method including condom, contraceptive diaphragm or cervix cap. The use of contraceptive or oral contraceptive containing hormones that may induce drug-drug interaction with the investigational product is not allowed during the study (with the exception of an oral contraceptive administered to cure menopausal symptoms, only if the dosage has been consistent for the past 8 weeks)

Sponsors & Collaborators

• Asan Medical Center: lead
• REDNVIA Co., Ltd.: collaborator

Study Sites (1)

Asan Medical Center

Seoul, South Korea

Location

Related Publications (8)

• Lindman BR, Clavel MA, Mathieu P, Iung B, Lancellotti P, Otto CM, Pibarot P. Calcific aortic stenosis. Nat Rev Dis Primers. 2016 Mar 3;2:16006. doi: 10.1038/nrdp.2016.6.

  PMID: 27188578 BACKGROUND

• Bonow RO, Greenland P. Population-wide trends in aortic stenosis incidence and outcomes. Circulation. 2015 Mar 17;131(11):969-71. doi: 10.1161/CIRCULATIONAHA.115.014846. Epub 2015 Feb 17. No abstract available.

  PMID: 25691712 BACKGROUND

• Choi B, Lee S, Kim SM, Lee EJ, Lee SR, Kim DH, Jang JY, Kang SW, Lee KU, Chang EJ, Song JK. Dipeptidyl Peptidase-4 Induces Aortic Valve Calcification by Inhibiting Insulin-Like Growth Factor-1 Signaling in Valvular Interstitial Cells. Circulation. 2017 May 16;135(20):1935-1950. doi: 10.1161/CIRCULATIONAHA.116.024270. Epub 2017 Feb 8.

  PMID: 28179397 BACKGROUND

• Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med. 1999 Jul 15;341(3):142-7. doi: 10.1056/NEJM199907153410302.

  PMID: 10403851 BACKGROUND

• Aronow WS, Ahn C, Shirani J, Kronzon I. Comparison of frequency of new coronary events in older subjects with and without valvular aortic sclerosis. Am J Cardiol. 1999 Feb 15;83(4):599-600, A8. doi: 10.1016/s0002-9149(98)00922-9.

  PMID: 10073870 BACKGROUND

• Pawade TA, Newby DE, Dweck MR. Calcification in Aortic Stenosis: The Skeleton Key. J Am Coll Cardiol. 2015 Aug 4;66(5):561-77. doi: 10.1016/j.jacc.2015.05.066.

  PMID: 26227196 BACKGROUND

• Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, Iung B, Lancellotti P, Lansac E, Rodriguez Munoz D, Rosenhek R, Sjogren J, Tornos Mas P, Vahanian A, Walther T, Wendler O, Windecker S, Zamorano JL; ESC Scientific Document Group. 2017 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2017 Sep 21;38(36):2739-2791. doi: 10.1093/eurheartj/ehx391. No abstract available.

  PMID: 28886619 BACKGROUND

• Brandenburg VM, Reinartz S, Kaesler N, Kruger T, Dirrichs T, Kramann R, Peeters F, Floege J, Keszei A, Marx N, Schurgers LJ, Koos R. Slower Progress of Aortic Valve Calcification With Vitamin K Supplementation: Results From a Prospective Interventional Proof-of-Concept Study. Circulation. 2017 May 23;135(21):2081-2083. doi: 10.1161/CIRCULATIONAHA.116.027011. No abstract available.

  PMID: 28533322 BACKGROUND

MeSH Terms

Interventions

4-(3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)piperazin-2-one

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: CMO, M.D, Ph.D, FACC, Department of Cardiology

Model Details: Randomized, open-label trial

Study Record Dates

• First Submitted: August 19, 2020
• First Posted: August 20, 2020
• Study Start: September 1, 2020
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2024
• Last Updated: August 20, 2020

Record last verified: 2020-08

Locations

KR (1)