The Alirocumab for Stopping Atherosclerosis Progression in Saphenous Vein Grafts (ASAP-SVG) Pilot Trial

Saphenous Vein Graft Atherosclerosis Clinical Trial

— ASAP-SVG  

Official title:

Effect of Alirocumab on Saphenous Vein Graft Atherosclerosis: The Alirocumab for Stopping Atherosclerosis Progression in Saphenous Vein Grafts (ASAP-SVG) Pilot Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03542110
• Other study ID #: ASAP-SVG, QR#32711/1
• Status: Terminated
• Phase: Phase 4
• Start date: August 4, 2018
• Est. completion date: July 31, 2020

Study information

• Verified date: September 2021
• Source: Minneapolis Heart Institute Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase IV, multi-center, double-blind, randomized, placebo- controlled study evaluating the effect of alirocumab on SVG atherosclerotic disease burden, as assessed by IVUS at baseline and following 78 weeks of treatment in subjects with at least one intermediate SVG lesion receiving optimal statin therapy. Subjects will be randomized 1:1 into 2 treatment groups: alirocumab 150 mg subcutaneously every 2 weeks or placebo subcutaneously every 2 weeks.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 46
• Est. completion date: July 31, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age 18 years or greater.

2. Willing and able to give informed consent. The patients must be able to comply with study procedures and follow-up.

3. Undergoing clinically-indicated coronary and SVG angiography.

4. Have at least one target saphenous vein graft with an intermediate SVG lesion (defined as a lesion with 30-60% angiographic diameter stenosis) amenable to examination with IVUS. The SVG should have no thrombus or ulceration and should not be considered responsible for the patient's clinical presentation and referral for angiography.

5. Receiving optimal statin therapy defined as use of a high intensity statin (atorvastatin 40-80 mg daily or rosuvastatin 20-40 mg daily), any statin therapy with achieved LDL-C level <70mg/dL, or maximally-tolerated statin dose for patients who are statin intolerant statin.

Exclusion Criteria:

1. Positive pregnancy test or breast-feeding.

2. Coexisting conditions that limit life expectancy to less than 18 months or that could affect a patient's compliance with the protocol.

3. Estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m2.

4. Severe peripheral arterial disease limiting vascular access.

5. History of allergic reaction to iodine-based contrast agents that cannot be premedicated.

6. Known hypersensitivity to alirocumab.

7. Any prior use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy.

Related Conditions & MeSH terms

• Atherosclerosis
• Saphenous Vein Graft Atherosclerosis

Intervention

Drug:
• Alirocumab 150 MG/ML subcutaneous injection
Single-dose, pre-filled, disposable, subcutaneous injection pen
• Matching Placebo subcutaneous injection
Single-dose, pre-filled, disposable, subcutaneous injection pen

Locations

Country	Name	City	State
United States	Atlanta VA Medical Center	Atlanta	Georgia
United States	Dallas VA Medical Center	Dallas	Texas
United States	Minneapolis Heart Institute/ Abbott North Western Hospital-Allina Health	Minneapolis	Minnesota
United States	San Francisco VA Medical Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Minneapolis Heart Institute Foundation	Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (16)

Alexander JH, Hafley G, Harrington RA, Peterson ED, Ferguson TB Jr, Lorenz TJ, Goyal A, Gibson M, Mack MJ, Gennevois D, Califf RM, Kouchoukos NT; PREVENT IV Investigators. Efficacy and safety of edifoligide, an E2F transcription factor decoy, for prevention of vein graft failure following coronary artery bypass graft surgery: PREVENT IV: a randomized controlled trial. JAMA. 2005 Nov 16;294(19):2446-54. — View Citation

Brilakis ES, Edson R, Bhatt DL, Goldman S, Holmes DR Jr, Rao SV, Shunk K, Rangan BV, Mavromatis K, Ramanathan K, Bavry AA, Garcia S, Latif F, Armstrong E, Jneid H, Conner TA, Wagner T, Karacsonyi J, Uyeda L, Ventura B, Alsleben A, Lu Y, Shih MC, Banerjee S; DIVA Trial Investigators. Drug-eluting stents versus bare-metal stents in saphenous vein grafts: a double-blind, randomised trial. Lancet. 2018 May 19;391(10134):1997-2007. doi: 10.1016/S0140-6736(18)30801-8. Epub 2018 May 11. — View Citation

Brilakis ES, Lee M, Mehilli J, Marmagkiolis K, Rodes-Cabau J, Sachdeva R, Kotsia A, Christopoulos G, Rangan BV, Mohammed A, Banerjee S. Saphenous vein graft interventions. Curr Treat Options Cardiovasc Med. 2014 May;16(5):301. doi: 10.1007/s11936-014-0301-x. — View Citation

DeFrances CJ, Lucas CA, Buie VC, Golosinskiy A. 2006 National Hospital Discharge Survey. Natl Health Stat Report. 2008 Jul 30;(5):1-20. — View Citation

Domanski MJ, Borkowf CB, Campeau L, Knatterud GL, White C, Hoogwerf B, Rosenberg Y, Geller NL. Prognostic factors for atherosclerosis progression in saphenous vein grafts: the postcoronary artery bypass graft (Post-CABG) trial. Post-CABG Trial Investigators. J Am Coll Cardiol. 2000 Nov 15;36(6):1877-83. — View Citation

Ellis SG, Brener SJ, DeLuca S, Tuzcu EM, Raymond RE, Whitlow PL, Topol EJ. Late myocardial ischemic events after saphenous vein graft intervention--importance of initially "nonsignificant" vein graft lesions. Am J Cardiol. 1997 Jun 1;79(11):1460-4. — View Citation

Fitzgibbon GM, Kafka HP, Leach AJ, Keon WJ, Hooper GD, Burton JR. Coronary bypass graft fate and patient outcome: angiographic follow-up of 5,065 grafts related to survival and reoperation in 1,388 patients during 25 years. J Am Coll Cardiol. 1996 Sep;28(3):616-26. — View Citation

Goldman S, Zadina K, Moritz T, Ovitt T, Sethi G, Copeland JG, Thottapurathu L, Krasnicka B, Ellis N, Anderson RJ, Henderson W; VA Cooperative Study Group #207/297/364. Long-term patency of saphenous vein and left internal mammary artery grafts after coronary artery bypass surgery: results from a Department of Veterans Affairs Cooperative Study. J Am Coll Cardiol. 2004 Dec 7;44(11):2149-56. — View Citation

Knatterud GL, White C, Geller NL, Campeau L, Forman SA, Domanski M, Forrester JS, Gobel FL, Herd JA, Hickey A, Hoogwerf BJ, Hunninghake DB, Terrin ML, Rosenberg Y. Angiographic changes in saphenous vein grafts are predictors of clinical outcomes. Am Heart J. 2003 Feb;145(2):262-9. — View Citation

Kotsia AP, Rangan BV, Christopoulos G, Coleman A, Roesle M, Cipher D, de Lemos JA, McGuire DK, Packer M, Banerjee S, Brilakis ES. Effect of Extended-Release Niacin on Saphenous Vein Graft Atherosclerosis: Insights from the Atherosclerosis Lesion Progression Intervention Using Niacin Extended Release in Saphenous Vein Grafts (ALPINE-SVG) Pilot Trial. J Invasive Cardiol. 2015 Oct;27(10):E204-10. — View Citation

Lichtenwalter C, de Lemos JA, Roesle M, Obel O, Holper EM, Haagen D, Saeed B, Iturbe JM, Shunk K, Bissett JK, Sachdeva R, Voudris VV, Karyofillis P, Kar B, Rossen J, Fasseas P, Berger P, Banerjee S, Brilakis ES. Clinical presentation and angiographic characteristics of saphenous vein graft failure after stenting: insights from the SOS (stenting of saphenous vein grafts) trial. JACC Cardiovasc Interv. 2009 Sep;2(9):855-60. doi: 10.1016/j.jcin.2009.06.014. — View Citation

Rodés-Cabau J, Bertrand OF, Larose E, Déry JP, Rinfret S, Bagur R, Proulx G, Nguyen CM, Côté M, Landcop MC, Boudreault JR, Rouleau J, Roy L, Gleeton O, Barbeau G, Noël B, Courtis J, Dagenais GR, Després JP, DeLarochellière R. Comparison of plaque sealing with paclitaxel-eluting stents versus medical therapy for the treatment of moderate nonsignificant saphenous vein graft lesions: the moderate vein graft lesion stenting with the taxus stent and intravascular ultrasound (VELETI) pilot trial. Circulation. 2009 Nov 17;120(20):1978-86. doi: 10.1161/CIRCULATIONAHA.109.874057. Epub 2009 Nov 2. — View Citation

Rodés-Cabau J, Bertrand OF, Larose E, Déry JP, Rinfret S, Urena M, Jerez M, Nombela-Franco L, Ribeiro HB, Allende R, Proulx G, Nguyen CM, Boudreault JR, Rouleau J, Roy L, Gleeton O, Barbeau G, Noël B, Côté M, Després JP, Dagenais GR, DeLarochellière R. Five-year follow-up of the plaque sealing with paclitaxel-eluting stents vs medical therapy for the treatment of intermediate nonobstructive saphenous vein graft lesions (VELETI) trial. Can J Cardiol. 2014 Jan;30(1):138-45. doi: 10.1016/j.cjca.2013.11.002. Epub 2013 Nov 6. — View Citation

Rodés-Cabau J, Facta A, Larose E, DeLarochellière R, Déry JP, Nguyen CM, Roy L, Proulx G, Gleeton O, Barbeau G, Noël B, Rouleau J, Boudreault JR, Bertrand OF. Predictors of aorto-saphenous vein bypass narrowing late after coronary artery bypass grafting. Am J Cardiol. 2007 Aug 15;100(4):640-5. Epub 2007 Jun 27. — View Citation

Sabik JF 3rd. Understanding saphenous vein graft patency. Circulation. 2011 Jul 19;124(3):273-5. doi: 10.1161/CIRCULATIONAHA.111.039842. — View Citation

Shroyer AL, Grover FL, Hattler B, Collins JF, McDonald GO, Kozora E, Lucke JC, Baltz JH, Novitzky D; Veterans Affairs Randomized On/Off Bypass (ROOBY) Study Group. On-pump versus off-pump coronary-artery bypass surgery. N Engl J Med. 2009 Nov 5;361(19):1827-37. doi: 10.1056/NEJMoa0902905. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nominal change in intermediate SVG lesion percent atheroma volume (PAV) from baseline to 78 weeks post randomization, as assessed by intravascular ultrasonography (IVUS).	To evaluate the effect of alirocumab on the change in burden of saphenous vein graft (SVG) atherosclerosis as measured by percent atheroma volume (PAV) in patients with intermediate SVG lesions who are undergoing clinically-indicated coronary angiography and are receiving optimal statin therapy.	78 weeks
Secondary	Nominal change in TAV and normalized TAV of an intermediate SVG lesion from baseline to 78 weeks	evaluate the effect of alirocumab on the change in total and normalized total atheroma volume (TAV) of an intermediate SVG lesion	78 weeks
Secondary	Angiographic failure of target SVG lesion from baseline to 78 weeks.	To evaluate the effect of alirocumab on the incidence of angiographic failure of an intermediate target SVG lesion.	78 weeks
Secondary	Incidence of target SVG failure and major adverse cardiac events.	To evaluate the effect of alirocumab on the incidence of target SVG failure (defined as the composite of death, myocardial infarction, and target lesion revascularization) and the incidence of major adverse cardiac events (MACE, defined as the composite of death, acute coronary syndrome, or coronary revascularization) during follow-up.	Randomization to 80 weeks