OPG and RANKL Plasma Level After Administration of Unfractionated Heparin (UFH) and Low-Molecular-Weight Heparin (LMWH) in Hemodialysis

NCT00669721 | Unknown DMC

• 1 other identifier: LWH-INT-79
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

A randomised, prospective, cross over study will be done to determine whether the anticoagulation therapy with UFH or LMWH used for hemodialysis sessions modifies osteoprotegerin and RANKL plasma levels.

Conditions

Renal Failure; Hemodialysis

Keywords

osteoprotegerin; RANKL; heparin; hemodialysis; anticoagulation; vascular calcification

Outcome Measures

Primary Outcomes (1)

• Levels of osteoprotegerin after administration of UFH or LMWH used as anticoagulant therapy for hemodialysis

  during and after dialysis sessions

Secondary Outcomes (1)

• Secondary aim of the study is to verify the safety of anticoagulation therapy with UFH and LMWH.

  during and after dialysis sessions

Study Arms (2)

A

EXPERIMENTAL

This patients start a run in period with LMWH schedule as hemodialysis circuit anticoagulation. Then they'll undergo hemodialysis with LMWH for a second period of two weeks: in this checking phase samples will be collected during the midweek hemodialysis sessions. After the checking phase the patients will be crossed to UFH schedule. A wash out period of two weeks with UFH will be done. At the end of this period two weeks of checking phase will starts.

Drug: law molecular weigth heparin

B

ACTIVE COMPARATOR

The patients randomized to receive UFH will start a run in period with this heparin schedule. Then they'll undergo hemodialysis with UFH for a second period of two weeks: in this checking phase samples will be collected during the midweek hemodialysis sessions. After the checking phase the patients will be crossed to LMWH. A wash out period of two weeks with UFH will be done. At the end of this period two weeks of checking phase will starts.

Drug: unfractioned heparin

Interventions

law molecular weigth heparin DRUG

administration of LMWH as anticoagulation for hemodialysis circuit;nadroparin is administred ad the dosage of 65 IU/kg on starting dialysis and in the arterial hemodialytic line after a washing phase with 2 litres of a heparin-free saline solution 0.9%.

Also known as: nadroparin

A

unfractioned heparin DRUG

administration of UFH as anticoagulation of hemodialysis circuit; standard heparin ( Sodic Heparin, Vister by Parke-Davis) 1500 IU on starting dialysis and 1500 ± 500 IU in continues intradialytic infusion per dialysis session

Also known as: standard heparin, Sodic Heparin

B

Eligibility Criteria

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

You may qualify if:

• hemodialysis patients with age \> 18 years on regular bicarbonate hemodialysis or hemodiafiltration treatment three times a week;
• clinical stability at least three months before the study started;

You may not qualify if:

• active gastrointestinal bleeding (one ore more positive hemoccult test in the last 8 weeks, melena or proctoraggia in the last 6 months )
• hemorrhagic stroke
• Myeloproliferative disorders
• Hereditary deficiency of coagulation factors, LAC phenomenon or antiphospholipid syndrome
• Malignant disease
• Patient submitted to antithrombotic prophylaxis with LMWH
• Immunosuppressive therapy
• Participation in other clinical trials

Sponsors & Collaborators

• IRCCS Azienda Ospedaliero-Universitaria di Bologna: lead

Study Sites (1)

St.Orsola University Hospital

Bologna, 40100, Italy

RECRUITING

Related Publications (18)

• Muir JM, Hirsh J, Weitz JI, Andrew M, Young E, Shaughnessy SG. A histomorphometric comparison of the effects of heparin and low-molecular-weight heparin on cancellous bone in rats. Blood. 1997 May 1;89(9):3236-42.

  PMID: 9129028 BACKGROUND

• Pettila V, Leinonen P, Markkola A, Hiilesmaa V, Kaaja R. Postpartum bone mineral density in women treated for thromboprophylaxis with unfractionated heparin or LMW heparin. Thromb Haemost. 2002 Feb;87(2):182-6.

  PMID: 11858475 BACKGROUND

• Irie A, Takami M, Kubo H, Sekino-Suzuki N, Kasahara K, Sanai Y. Heparin enhances osteoclastic bone resorption by inhibiting osteoprotegerin activity. Bone. 2007 Aug;41(2):165-74. doi: 10.1016/j.bone.2007.04.190. Epub 2007 May 5.

  PMID: 17560185 BACKGROUND

• Vik A, Brodin E, Sveinbjornsson B, Hansen JB. Heparin induces mobilization of osteoprotegerin into the circulation. Thromb Haemost. 2007 Jul;98(1):148-54.

  PMID: 17598007 BACKGROUND

• Collin-Osdoby P. Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin. Circ Res. 2004 Nov 26;95(11):1046-57. doi: 10.1161/01.RES.0000149165.99974.12.

  PMID: 15564564 BACKGROUND

• Vega D, Maalouf NM, Sakhaee K. CLINICAL Review #: the role of receptor activator of nuclear factor-kappaB (RANK)/RANK ligand/osteoprotegerin: clinical implications. J Clin Endocrinol Metab. 2007 Dec;92(12):4514-21. doi: 10.1210/jc.2007-0646. Epub 2007 Sep 25.

  PMID: 17895323 BACKGROUND

• Orita Y, Yamamoto H, Kohno N, Sugihara M, Honda H, Kawamata S, Mito S, Soe NN, Yoshizumi M. Role of osteoprotegerin in arterial calcification: development of new animal model. Arterioscler Thromb Vasc Biol. 2007 Sep;27(9):2058-64. doi: 10.1161/ATVBAHA.107.147868. Epub 2007 Jul 5.

  PMID: 17615383 BACKGROUND

• Nitta K, Akiba T, Uchida K, Otsubo S, Takei T, Yumura W, Kabaya T, Nihei H. Serum osteoprotegerin levels and the extent of vascular calcification in haemodialysis patients. Nephrol Dial Transplant. 2004 Jul;19(7):1886-9. doi: 10.1093/ndt/gfh263. Epub 2004 May 5.

  PMID: 15128884 BACKGROUND

• Schoppet M, Shroff RC, Hofbauer LC, Shanahan CM. Exploring the biology of vascular calcification in chronic kidney disease: what's circulating? Kidney Int. 2008 Feb;73(4):384-90. doi: 10.1038/sj.ki.5002696. Epub 2007 Nov 28.

  PMID: 18046319 BACKGROUND

• Zannettino AC, Holding CA, Diamond P, Atkins GJ, Kostakis P, Farrugia A, Gamble J, To LB, Findlay DM, Haynes DR. Osteoprotegerin (OPG) is localized to the Weibel-Palade bodies of human vascular endothelial cells and is physically associated with von Willebrand factor. J Cell Physiol. 2005 Aug;204(2):714-23. doi: 10.1002/jcp.20354.

  PMID: 15799029 BACKGROUND

• Standal T, Seidel C, Hjertner O, Plesner T, Sanderson RD, Waage A, Borset M, Sundan A. Osteoprotegerin is bound, internalized, and degraded by multiple myeloma cells. Blood. 2002 Oct 15;100(8):3002-7. doi: 10.1182/blood-2002-04-1190.

  PMID: 12351414 BACKGROUND

• Theoleyre S, Kwan Tat S, Vusio P, Blanchard F, Gallagher J, Ricard-Blum S, Fortun Y, Padrines M, Redini F, Heymann D. Characterization of osteoprotegerin binding to glycosaminoglycans by surface plasmon resonance: role in the interactions with receptor activator of nuclear factor kappaB ligand (RANKL) and RANK. Biochem Biophys Res Commun. 2006 Aug 25;347(2):460-7. doi: 10.1016/j.bbrc.2006.06.120. Epub 2006 Jun 30.

  PMID: 16828054 BACKGROUND

• Valentin S, Larnkjer A, Ostergaard P, Nielsen JI, Nordfang O. Characterization of the binding between tissue factor pathway inhibitor and glycosaminoglycans. Thromb Res. 1994 Jul 15;75(2):173-83. doi: 10.1016/0049-3848(94)90066-3.

  PMID: 7974391 BACKGROUND

• Hansen JB, Sandset PM, Huseby KR, Huseby NE, Nordoy A. Depletion of intravascular pools of tissue factor pathway inhibitor (TFPI) during repeated or continuous intravenous infusion of heparin in man. Thromb Haemost. 1996 Nov;76(5):703-9.

  PMID: 8950777 BACKGROUND

• Deruelle P, Coulon C. The use of low-molecular-weight heparins in pregnancy--how safe are they? Curr Opin Obstet Gynecol. 2007 Dec;19(6):573-7. doi: 10.1097/GCO.0b013e3282f10e33.

  PMID: 18007136 RESULT

• Folwarczna J, Sliwinski L, Janiec W, Pikul M. Effects of standard heparin and low-molecular-weight heparins on the formation of murine osteoclasts in vitro. Pharmacol Rep. 2005 Sep-Oct;57(5):635-45.

  PMID: 16227647 RESULT

• Vescini F, Buffa A, Sinicropi G. Osteoprotegerina RANKL e RANK nella regolazione dell'ostoclastogenesi. Riv It Biol Med 22: 64-67, 2002.

  RESULT

• Natale P, Palmer SC, Ruospo M, Longmuir H, Dodds B, Prasad R, Batt TJ, Jose MD, Strippoli GF. Anticoagulation for people receiving long-term haemodialysis. Cochrane Database Syst Rev. 2024 Jan 8;1(1):CD011858. doi: 10.1002/14651858.CD011858.pub2.

  PMID: 38189593 DERIVED

MeSH Terms

Conditions

Renal Insufficiency; Vascular Calcification

Interventions

Nadroparin

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Calcinosis; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Sergio Stefoni, Prof

  St.orsola University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 25, 2008
• First Posted: April 30, 2008
• Study Start: March 1, 2008
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2008
• Last Updated: April 30, 2008

Record last verified: 2008-04

Locations

IT (1)