High-intensity Atorvastatin for Arteriovenous Fistula Failure (HAFF): A Feasibility Pilot Study

NCT03188978 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: HAFF
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Primary failure is the most common complication of newly created arteriovenous fistulas (AVFs) and an important contributor to end stage renal disease (ESRD) patients' morbidity and mortality. Recently, the investigators have found that high intensity atorvastatin (40 mg/day) reduces AVF primary failure significantly when compared to other statins or no statin treatment in three separate prospective and retrospective studies done in collaboration with the University of Miami. Based on these findings and considering the necessity for a therapy to improve AVF maturation rates, the investigators propose the realization of a feasibility pilot double blinded randomized controlled trial (RCT). In this study, a total of 50 patients will be randomly allocated to receive high intensity atorvastatin (40 mg daily) or placebo starting at two weeks before surgery and until the end of the observational period (6 weeks after surgery). Present trial will reveal crucial feasibility information such as the appropriateness of the eligibility criteria, patient recruitment and retention rates, compliance, adverse events, efficacy of patient follow-ups, and readiness of the facilities and involved personnel; while having as a secondary endpoint the predictive measurements of diameter and AVF blood flow 6 weeks after fistula creation useful for the estimation of the probable effect of proposed intervention. Here, the investigators aim to pave the way for a future multicenter Phase II RCT seeking to prove the efficacy of atorvastatin therapy as a perioperative intervention to reduce AVF primary failure.

Conditions

Primary Arteriovenous Fistula Failure

Outcome Measures

Primary Outcomes (4)

• Patient recruitment rate (in percent)

  The patient recruitment rate (in percent) is an important parameter to evaluate the feasibility of the study and to plan future Phase II trials.

  104 weeks

• Patient retention rate (in percent)

  The patient retention rate (in percent) is an important parameter to evaluate the feasibility of the study and to plan future Phase II trials.

  104 weeks

• Patient compliance (in percent)

  The patient compliance (in percent) is an important parameter to evaluate the feasibility of the study and to plan future Phase II trials.

  104 weeks

• Rate of adverse events (in percent)

  The rate of adverse events (in percent) is an important parameter to evaluate the safety of the study and it is important to plan future Phase II trials.

  104 weeks

Secondary Outcomes (2)

• Ultrasonographic measurement of AVF blood flow (in milliliter per minute).

  104 weeks

• Ultrasonographic measurements of diameter (in millimeters).

  104 weeks

Study Arms (2)

Treatment

EXPERIMENTAL

Atorvastatin 40mg once daily orally for 8 weeks starting 2 weeks before AVF creation

Drug: Atorvastatin 40mg

Placebo

PLACEBO COMPARATOR

1 tablet once daily orally for 8 weeks starting 2 weeks before AVF creation

Other: Placebo

Interventions

Atorvastatin 40mg DRUG

one 40mg tablet daily for 8 weeks starting 2 weeks before the AVF creation.

Also known as: Lipitor 40mg tablets

Treatment

Placebo OTHER

one tablet daily for 8 weeks starting 2 weeks before the AVF creation.

Placebo

Eligibility Criteria

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

You may qualify if:

• age\>18 years of age;
• stage 4 or 5 CKD;
• one-stage AVF surgery is planned (radiocephalic or brachiocephalic);
• and statin-naïve or at least 6 months from last statin use.

You may not qualify if:

• revision of an existing AVF instead of a de novo access;
• known intolerance or hypersensitivity to statins;
• active liver disease;
• elevation in AST, ALT or CPK of more than 3 times the upper limit of normal;
• baseline LDL\<40 mg/dL;
• coadministration of strong interacting drugs;
• any condition in which statins are contraindicated;
• involvement in another trial where the intervention may confound the outcome of this trial.

Sponsors & Collaborators

• Albany Medical College: lead

Study Sites (1)

Albany Medical College

Albany, New York, 12208, United States

Location

Related Publications (19)

• Huijbregts HJ, Bots ML, Wittens CH, Schrama YC, Moll FL, Blankestijn PJ; CIMINO study group. Hemodialysis arteriovenous fistula patency revisited: results of a prospective, multicenter initiative. Clin J Am Soc Nephrol. 2008 May;3(3):714-9. doi: 10.2215/CJN.02950707. Epub 2008 Feb 6.

  PMID: 18256379 BACKGROUND

• Schinstock CA, Albright RC, Williams AW, Dillon JJ, Bergstralh EJ, Jenson BM, McCarthy JT, Nath KA. Outcomes of arteriovenous fistula creation after the Fistula First Initiative. Clin J Am Soc Nephrol. 2011 Aug;6(8):1996-2002. doi: 10.2215/CJN.11251210. Epub 2011 Jul 7.

  PMID: 21737851 BACKGROUND

• Bashar K, Zafar A, Elsheikh S, Healy DA, Clarke-Moloney M, Casserly L, Burke PE, Kavanagh EG, Walsh SR. Predictive parameters of arteriovenous fistula functional maturation in a population of patients with end-stage renal disease. PLoS One. 2015 Mar 13;10(3):e0119958. doi: 10.1371/journal.pone.0119958. eCollection 2015.

  PMID: 25768440 BACKGROUND

• Pisoni R, Barker-Finkel J, Allo M. Statin therapy is not associated with improved vascular access outcomes. Clin J Am Soc Nephrol. 2010 Aug;5(8):1447-50. doi: 10.2215/CJN.02740310. Epub 2010 May 27.

  PMID: 20507962 BACKGROUND

• Martinez L, Duque JC, Escobar LA, Tabbara M, Asif A, Fayad F, Vazquez-Padron RI, Salman LH. Distinct impact of three different statins on arteriovenous fistula outcomes: a retrospective analysis. J Vasc Access. 2016 Nov 2;17(6):471-476. doi: 10.5301/jva.5000612. Epub 2016 Oct 15.

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• Robbin ML, Greene T, Cheung AK, Allon M, Berceli SA, Kaufman JS, Allen M, Imrey PB, Radeva MK, Shiu YT, Umphrey HR, Young CJ; Hemodialysis Fistula Maturation Study Group. Arteriovenous Fistula Development in the First 6 Weeks after Creation. Radiology. 2016 May;279(2):620-9. doi: 10.1148/radiol.2015150385. Epub 2015 Dec 22.

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  PMID: 26092476 BACKGROUND

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  PMID: 15822172 BACKGROUND

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  PMID: 12590901 BACKGROUND

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  PMID: 17126678 BACKGROUND

• Tabbara M, Duque JC, Martinez L, Escobar LA, Wu W, Pan Y, Fernandez N, Velazquez OC, Jaimes EA, Salman LH, Vazquez-Padron RI. Pre-existing and Postoperative Intimal Hyperplasia and Arteriovenous Fistula Outcomes. Am J Kidney Dis. 2016 Sep;68(3):455-64. doi: 10.1053/j.ajkd.2016.02.044. Epub 2016 Mar 22.

  PMID: 27012909 BACKGROUND

• Duque JC, Martinez L, Tabbara M, Dvorquez D, Mehandru SK, Asif A, Vazquez-Padron RI, Salman LH. Arteriovenous fistula maturation in patients with permanent access created prior to or after hemodialysis initiation. J Vasc Access. 2017 May 15;18(3):185-191. doi: 10.5301/jva.5000662. Epub 2017 Feb 15.

  PMID: 28218361 BACKGROUND

• Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S1-45. doi: 10.1161/01.cir.0000437738.63853.7a. Epub 2013 Nov 12. No abstract available.

  PMID: 24222016 BACKGROUND

• Foundation NK. KDOQI clinical practice guidelines and clinical practice recommendations for 2006 updates: hemodialysis adequacy, peritoneal dialysis adequacy and vascular access. Am J Kidney Dis. 2006;48(Suppl 1):S1-S322.

  BACKGROUND

• Dember LM, Imrey PB, Beck GJ, Cheung AK, Himmelfarb J, Huber TS, Kusek JW, Roy-Chaudhury P, Vazquez MA, Alpers CE, Robbin ML, Vita JA, Greene T, Gassman JJ, Feldman HI; Hemodialysis Fistula Maturation Study Group. Objectives and design of the hemodialysis fistula maturation study. Am J Kidney Dis. 2014 Jan;63(1):104-12. doi: 10.1053/j.ajkd.2013.06.024. Epub 2013 Aug 28.

  PMID: 23992885 BACKGROUND

• Gupta SK. Intention-to-treat concept: A review. Perspect Clin Res. 2011 Jul;2(3):109-12. doi: 10.4103/2229-3485.83221.

  PMID: 21897887 BACKGROUND

• Robbin ML, Chamberlain NE, Lockhart ME, Gallichio MH, Young CJ, Deierhoi MH, Allon M. Hemodialysis arteriovenous fistula maturity: US evaluation. Radiology. 2002 Oct;225(1):59-64. doi: 10.1148/radiol.2251011367.

  PMID: 12354984 BACKGROUND

MeSH Terms

Interventions

Atorvastatin

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Loay Salman, MD,MBA

  Albany Medical College

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: June 12, 2017
• First Posted: June 16, 2017
• Study Start: November 1, 2018
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: January 18, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)