Vitamin K Supplementation in Patients on Hemodialysis

NCT02324686 | Completed Phase 2

• 1 other identifier: 14-8200
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether vitamin K supplementation will improve anticoagulation control in patients on hemodialysis taking warfarin for atrial fibrillation. Patients who participate will receive vitamin K1 three times a week on dialysis days for a period of four months. INR levels collected during this period will be compared to the four month period prior to receiving the vitamin K1 to determine if vitamin K improves the standard deviation of INRs and time in therapeutic range.

Conditions

End Stage Renal Failure on Dialysis; Atrial Fibrillation

Keywords

Warfarin; International Normalized Ratio; Vitamin K

Outcome Measures

Primary Outcomes (1)

• INR stability (standard deviation of INR values)

  standard deviation of INR values, 4 months before and 4 months after the intervention

  4 months before and 4 months after intervention

Secondary Outcomes (2)

• Time in Therapeutic Range (Percentage of time INR levels within range)

  4 months before and 4 months after intervention

• Adverse events

  4 months before and 4 months after intervention

Study Arms (1)

Vitamin K1

OTHER

Vitamin K1 400 mcg orally three times a week on dialysis days for four months

Drug: vitamin K1

Interventions

vitamin K1 DRUG

Vitamin K1 400 mcg orally three times a week on dialysis days for four months

Also known as: phytonadione

Vitamin K1

Eligibility Criteria

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

You may qualify if:

• greater than 18 years of age
• Receiving in-house hemodialysis for at least 6 months
• Previously diagnosed with atrial fibrillation
• On warfarin for at least 6 months with a target INR of 2-3

You may not qualify if:

• are unable to provide informed consent
• have a mechanical heart valve
• are receiving supplements containing vitamin K
• have a known hypersensitivity to vitamin K

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (25)

• Reinecke H, Engelbertz C, Schabitz WR. Preventing stroke in patients with chronic kidney disease and atrial fibrillation: benefit and risks of old and new oral anticoagulants. Stroke. 2013 Oct;44(10):2935-41. doi: 10.1161/STROKEAHA.113.001701. Epub 2013 Sep 5. No abstract available.

  PMID: 24008579 BACKGROUND

• Sood MM, Komenda P, Sood AR, Rigatto C, Bueti J. The intersection of risk and benefit: is warfarin anticoagulation suitable for atrial fibrillation in patients on hemodialysis? Chest. 2009 Oct;136(4):1128-1133. doi: 10.1378/chest.09-0730.

  PMID: 19809054 BACKGROUND

• Shah M, Avgil Tsadok M, Jackevicius CA, Essebag V, Eisenberg MJ, Rahme E, Humphries KH, Tu JV, Behlouli H, Guo H, Pilote L. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation. 2014 Mar 18;129(11):1196-203. doi: 10.1161/CIRCULATIONAHA.113.004777. Epub 2014 Jan 22.

  PMID: 24452752 BACKGROUND

• Marinigh R, Lane DA, Lip GY. Severe renal impairment and stroke prevention in atrial fibrillation: implications for thromboprophylaxis and bleeding risk. J Am Coll Cardiol. 2011 Mar 22;57(12):1339-48. doi: 10.1016/j.jacc.2010.12.013.

  PMID: 21414530 BACKGROUND

• Skanes AC, Healey JS, Cairns JA, Dorian P, Gillis AM, McMurtry MS, Mitchell LB, Verma A, Nattel S; Canadian Cardiovascular Society Atrial Fibrillation Guidelines Committee. Focused 2012 update of the Canadian Cardiovascular Society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control. Can J Cardiol. 2012 Mar-Apr;28(2):125-36. doi: 10.1016/j.cjca.2012.01.021.

  PMID: 22433576 BACKGROUND

• January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC Jr, Conti JB, Ellinor PT, Ezekowitz MD, Field ME, Murray KT, Sacco RL, Stevenson WG, Tchou PJ, Tracy CM, Yancy CW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2014 Dec 2;64(21):e1-76. doi: 10.1016/j.jacc.2014.03.022. Epub 2014 Mar 28. No abstract available.

  PMID: 24685669 BACKGROUND

• Sood MM, Larkina M, Thumma JR, Tentori F, Gillespie BW, Fukuhara S, Mendelssohn DC, Chan K, de Sequera P, Komenda P, Rigatto C, Robinson BM. Major bleeding events and risk stratification of antithrombotic agents in hemodialysis: results from the DOPPS. Kidney Int. 2013 Sep;84(3):600-8. doi: 10.1038/ki.2013.170. Epub 2013 May 15.

  PMID: 23677245 BACKGROUND

• Clase CM, Holden RM, Sood MM, Rigatto C, Moist LM, Thomson BK, Mann JF, Zimmerman DL. Should patients with advanced chronic kidney disease and atrial fibrillation receive chronic anticoagulation? Nephrol Dial Transplant. 2012 Oct;27(10):3719-24. doi: 10.1093/ndt/gfs346.

  PMID: 23114898 BACKGROUND

• Gebuis EP, Rosendaal FR, van Meegen E, van der Meer FJ. Vitamin K1 supplementation to improve the stability of anticoagulation therapy with vitamin K antagonists: a dose-finding study. Haematologica. 2011 Apr;96(4):583-9. doi: 10.3324/haematol.2010.035162. Epub 2010 Dec 29.

  PMID: 21193422 BACKGROUND

• Sconce E, Avery P, Wynne H, Kamali F. Vitamin K supplementation can improve stability of anticoagulation for patients with unexplained variability in response to warfarin. Blood. 2007 Mar 15;109(6):2419-23. doi: 10.1182/blood-2006-09-049262. Epub 2006 Nov 16.

  PMID: 17110451 BACKGROUND

• Cushman M, Booth SL, Possidente CJ, Davidson KW, Sadowski JA, Bovill EG. The association of vitamin K status with warfarin sensitivity at the onset of treatment. Br J Haematol. 2001 Mar;112(3):572-7. doi: 10.1046/j.1365-2141.2001.02635.x.

  PMID: 11260056 BACKGROUND

• Sconce E, Khan T, Mason J, Noble F, Wynne H, Kamali F. Patients with unstable control have a poorer dietary intake of vitamin K compared to patients with stable control of anticoagulation. Thromb Haemost. 2005 May;93(5):872-5. doi: 10.1160/TH04-12-0773.

  PMID: 15886802 BACKGROUND

• Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ, Svensson PJ, Veenstra DL, Crowther M, Guyatt GH. Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e152S-e184S. doi: 10.1378/chest.11-2295.

  PMID: 22315259 BACKGROUND

• Lam J, Schulman S, Witt DM, Vandvik PO, Qayyum F, Holbrook AM. Anticoagulation control with daily low-dose vitamin k to reduce clinically adverse outcomes and international normalized ratio variability: a systematic review and meta-analysis. Pharmacotherapy. 2013 Nov;33(11):1184-90. doi: 10.1002/phar.1302. Epub 2013 Jun 6.

  PMID: 23744743 BACKGROUND

• Rombouts EK, Rosendaal FR, Van Der Meer FJ. Daily vitamin K supplementation improves anticoagulant stability. J Thromb Haemost. 2007 Oct;5(10):2043-8. doi: 10.1111/j.1538-7836.2007.02715.x. Epub 2007 Jul 31.

  PMID: 17666020 BACKGROUND

• Westenfeld R, Krueger T, Schlieper G, Cranenburg EC, Magdeleyns EJ, Heidenreich S, Holzmann S, Vermeer C, Jahnen-Dechent W, Ketteler M, Floege J, Schurgers LJ. Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. Am J Kidney Dis. 2012 Feb;59(2):186-95. doi: 10.1053/j.ajkd.2011.10.041. Epub 2011 Dec 9.

  PMID: 22169620 BACKGROUND

• Cranenburg EC, Schurgers LJ, Uiterwijk HH, Beulens JW, Dalmeijer GW, Westerhuis R, Magdeleyns EJ, Herfs M, Vermeer C, Laverman GD. Vitamin K intake and status are low in hemodialysis patients. Kidney Int. 2012 Sep;82(5):605-10. doi: 10.1038/ki.2012.191. Epub 2012 May 30.

  PMID: 22648294 BACKGROUND

• Krueger T, Schlieper G, Schurgers L, Cornelis T, Cozzolino M, Jacobi J, Jadoul M, Ketteler M, Rump LC, Stenvinkel P, Westenfeld R, Wiecek A, Reinartz S, Hilgers RD, Floege J. Vitamin K1 to slow vascular calcification in haemodialysis patients (VitaVasK trial): a rationale and study protocol. Nephrol Dial Transplant. 2014 Sep;29(9):1633-8. doi: 10.1093/ndt/gft459. Epub 2013 Nov 26.

  PMID: 24285427 BACKGROUND

• Ford SK, Misita CP, Shilliday BB, Malone RM, Moore CG, Moll S. Prospective study of supplemental vitamin K therapy in patients on oral anticoagulants with unstable international normalized ratios. J Thromb Thrombolysis. 2007 Aug;24(1):23-7. doi: 10.1007/s11239-007-0014-z. Epub 2007 Feb 24.

  PMID: 17323135 BACKGROUND

• Reese AM, Farnett LE, Lyons RM, Patel B, Morgan L, Bussey HI. Low-dose vitamin K to augment anticoagulation control. Pharmacotherapy. 2005 Dec;25(12):1746-51. doi: 10.1592/phco.2005.25.12.1746.

  PMID: 16305294 BACKGROUND

• Majeed H, Rodger M, Forgie M, Carrier M, Taljaard M, Scarvelis D, Gonsalves C, Rodriguez RA, Wells PS. Effect of 200muG/day of vitamin K1 on the variability of anticoagulation control in patients on warfarin: a randomized controlled trial. Thromb Res. 2013 Sep;132(3):329-35. doi: 10.1016/j.thromres.2013.07.019. Epub 2013 Jul 29.

  PMID: 23953594 BACKGROUND

• Schurgers LJ, Shearer MJ, Hamulyak K, Stocklin E, Vermeer C. Effect of vitamin K intake on the stability of oral anticoagulant treatment: dose-response relationships in healthy subjects. Blood. 2004 Nov 1;104(9):2682-9. doi: 10.1182/blood-2004-04-1525. Epub 2004 Jul 1.

  PMID: 15231565 BACKGROUND

• Schulman S, Angeras U, Bergqvist D, Eriksson B, Lassen MR, Fisher W; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost. 2010 Jan;8(1):202-4. doi: 10.1111/j.1538-7836.2009.03678.x. Epub 2009 Oct 30.

  PMID: 19878532 BACKGROUND

• White HD, Gruber M, Feyzi J, Kaatz S, Tse HF, Husted S, Albers GW. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med. 2007 Feb 12;167(3):239-45. doi: 10.1001/archinte.167.3.239.

  PMID: 17296878 BACKGROUND

• Juurlink DN. Drug interactions with warfarin: what clinicians need to know. CMAJ. 2007 Aug 14;177(4):369-71. doi: 10.1503/cmaj.070946. No abstract available.

  PMID: 17698826 BACKGROUND

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Vitamin K 1

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Vitamin K; Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phytol; Diterpenes; Terpenes; Quinones; Polycyclic Compounds

Study Officials

• Marisa Battistella

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2014
• First Posted: December 24, 2014
• Study Start: January 1, 2014
• Primary Completion: December 18, 2017
• Study Completion: December 18, 2017
• Last Updated: February 6, 2018

Record last verified: 2016-05

Locations

CA (1)