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

NCT03542110 | Terminated Phase 4 DMC FDA Drug

• 1 other identifier: ASAP-SVG, QR#32711/1
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Saphenous Vein Graft Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Nominal change in TAV and normalized TAV of an intermediate SVG lesion from baseline to 78 weeks

  78 weeks

• Angiographic failure of target SVG lesion from baseline to 78 weeks.

  78 weeks

• Incidence of target SVG failure and major adverse cardiac events.

  Randomization to 80 weeks

Study Arms (2)

Alirocumab 150 MG/ML subcutaneous injection

ACTIVE COMPARATOR

Alirocumab 150 mg subcutaneously every 2 weeks

Drug: Alirocumab 150 MG/ML subcutaneous injection

Matching Placebo subcutaneous injection

PLACEBO COMPARATOR

Matching placebo subcutaneously every 2 weeks

Drug: Matching Placebo subcutaneous injection

Interventions

Alirocumab 150 MG/ML subcutaneous injection DRUG

Single-dose, pre-filled, disposable, subcutaneous injection pen

Also known as: Praluent, Study Drug

Alirocumab 150 MG/ML subcutaneous injection

Matching Placebo subcutaneous injection DRUG

Single-dose, pre-filled, disposable, subcutaneous injection pen

Also known as: Placebo, Study Drug

Matching Placebo subcutaneous injection

Eligibility Criteria

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

You may qualify if:

• Age 18 years or greater.
• Willing and able to give informed consent. The patients must be able to comply with study procedures and follow-up.
• Undergoing clinically-indicated coronary and SVG angiography.
• 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.
• 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.

You may not qualify if:

• Positive pregnancy test or breast-feeding.
• Coexisting conditions that limit life expectancy to less than 18 months or that could affect a patient's compliance with the protocol.
• Estimated glomerular filtration rate (eGFR) \<30 ml/min/1.73m2.
• Severe peripheral arterial disease limiting vascular access.
• History of allergic reaction to iodine-based contrast agents that cannot be premedicated.
• Known hypersensitivity to alirocumab.
• Any prior use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy.

Sponsors & Collaborators

• Minneapolis Heart Institute Foundation: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (4)

San Francisco VA Medical Center

San Francisco, California, 94121, United States

Location

Atlanta VA Medical Center

Atlanta, Georgia, 30033, United States

Location

Minneapolis Heart Institute/ Abbott North Western Hospital-Allina Health

Minneapolis, Minnesota, 55407, United States

Location

Dallas VA Medical Center

Dallas, Texas, 75216, United States

Location

Related Publications (16)

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• 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. doi: 10.1001/jama.294.19.2446.

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• Sabik JF 3rd. Understanding saphenous vein graft patency. Circulation. 2011 Jul 19;124(3):273-5. doi: 10.1161/CIRCULATIONAHA.111.039842. No abstract available.

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• 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.

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• 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. doi: 10.1016/j.jacc.2004.08.064.

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• 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. doi: 10.1016/0735-1097(96)00206-9.

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• 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.

  PMID: 19778774 BACKGROUND

• 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.

  PMID: 24643432 BACKGROUND

• 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. doi: 10.1016/s0002-9149(97)00171-9.

  PMID: 9185633 BACKGROUND

• 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. doi: 10.1067/mhj.2003.113.

  PMID: 12595843 BACKGROUND

• Rodes-Cabau J, Facta A, Larose E, DeLarochelliere R, Dery JP, Nguyen CM, Roy L, Proulx G, Gleeton O, Barbeau G, Noel 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. doi: 10.1016/j.amjcard.2007.03.080. Epub 2007 Jun 27.

  PMID: 17697821 BACKGROUND

• Rodes-Cabau J, Bertrand OF, Larose E, Dery JP, Rinfret S, Bagur R, Proulx G, Nguyen CM, Cote M, Landcop MC, Boudreault JR, Rouleau J, Roy L, Gleeton O, Barbeau G, Noel B, Courtis J, Dagenais GR, Despres JP, DeLarochelliere 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.

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• Rodes-Cabau J, Bertrand OF, Larose E, Dery 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, Noel B, Cote M, Despres JP, Dagenais GR, DeLarochelliere 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.

  PMID: 24365196 BACKGROUND

• 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.

  PMID: 26429851 BACKGROUND

• 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.

  PMID: 29759512 BACKGROUND

MeSH Terms

Interventions

alirocumab; Injections, Subcutaneous; Drug Evaluation

Intervention Hierarchy (Ancestors)

Injections; Drug Administration Routes; Drug Therapy; Therapeutics; Drug Development; Investigative Techniques; Evaluation Studies as Topic

Study Officials

• Emmanouil S Brilakis, MD, PhD

  Minneapolis Heart Institute and Foundation/ Abbott Northwestern Hospital-Allina Health

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2018
• First Posted: May 31, 2018
• Study Start: August 4, 2018
• Primary Completion: June 30, 2020
• Study Completion: July 31, 2020
• Last Updated: September 16, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)