A Study of Factor Inhibitors in Adult Patients With Hemophilia and Von Willebrand's Disease in Upper Egypt

Hemophilia Clinical Trial

Official title:

A Study of Factor Inhibitors in Adult Patients With Hemophilia and Von Willebrand's Disease in Upper Egypt

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04106323
• Other study ID #: SKhaled20
• Status: Not yet recruiting
• Start date: May 10, 2020
• Est. completion date: August 20, 2021

Study information

• Verified date: October 2019
• Source: Assiut University
• Contact: Safaa A Khaled, Ass. Prof.
• Phone: 01064170058
• Email: safaakhaled2003[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Hemophilia A and B are bleeding disorders caused by deficiency of factor VIII and IX, respectively. The deficiency of one of these coagulation factors is due to a mutation on the X chromosome. Accordingly replacement of the deficient factor is currently the main treatment for these disorders. The most disappointing complication of replacement therapy in hemophilia is the development of inhibitors. Unlike haemophilia , inhibitor development in patients with V Willebrand's Disease (VWD) is a rare complication of treatment. Studies on inhibitors whether on hemophilia or VWD are limited in our region.

This study aims to

1. To estimate the frequency of factor inhibitors in hemophilia and VWD patients in our region.

2. To investigate modifiable risk factors associated with development of inhibitors in both diseases.

3. To correlate the level of inhibitor with the clinical presentation of the patients.

4. To assess influence of factor inhibitors on quality of life in patients who developed factor inhibitors in both diseases.

Description:

Individuals with hemophilia are deficient in one of the clotting factor proteins that are vital in the formation of a clot. Classic hemophilia or hemophilia A is a deficiency of factor VIII, while Christmas Disease or Hemophilia B is a deficiency of factor IX. The prevalence of hemophilia A or B varies in different countries and geographic regions.

Patients with either type of hemophilia are at risk for prolonged bleeding, replacement of the deficient protein is the main therapy . The most serious complication of replacement therapy in hemophilia is the development of inhibitors.An inhibitor is a polyclonal high‑affinity immunoglobulin G (IgG) that is directed against the clotting factorI protein. These antibodies can be either inhibitory or non inhibitory.

Inhibitors neutralize the administered clotting factor so that bleeding does not stop. Inhibitors are the most significant risk factor for morbidity and mortality associated with hemophilia, and patients with inhibitors present complex patient management challenges.

Few studies investigated development of factor inhibitor in Egyptian patients, however most of them concentrated on pediatric patients, also data regarding factor inhibitors in Upper Egypt was limited.

VonWillebrand's disease is a bleeding disorder caused by deficiency of VWF. The treatment of VWD is somewhat similar to that of patients with hemophilia which consists of infusions to replace the missing factors as on demand regimen using plasma derived (PD) products which contains both FVIII and VWF. Furthermore, many of the patients are currently on some form of prophylaxis to eliminate or decrease the frequency of bleeding episodes.

Nearly, 7.5 % of VWD patients develop inhibitors to VWF becoming non- responsive to replacement therapy, and prone to develop severe anaphylactic and life threatening reactions when exposed to any product that contains VWF.

Unlike hemophilia clinical presentation of VWD patients who developed inhibitors is not serious.

Again data on factor inhibitors in VWD is deficient in many countries worldwide particularly Egypt . Investigators assumed that this is the first study that well assess factor inhibitors in VWD in Upper Egypt.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: August 20, 2021
• Est. primary completion date: November 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Patients diagnosed congenital hemophilia A, Christmas disease, and VWD

Exclusion Criteria

• Patients diagnosed with acquired hemophilia

• Patients below 18 years

• Patients with other bleeding tendencies

Related Conditions & MeSH terms

• Christmas Disease
• Hemophilia
• Hemophilia A
• Hemophilia B
• Von Willebrand Diseases

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Safaa AA Khaled

References & Publications (11)

Duncan E, Collecutt M, Street A. Nijmegen-Bethesda assay to measure factor VIII inhibitors. Methods Mol Biol. 2013;992:321-33. doi: 10.1007/978-1-62703-339-8_24. — View Citation

Ghosh K, Shukla R. Future of Haemophilia Research in India. Indian J Hematol Blood Transfus. 2017 Dec;33(4):451-452. doi: 10.1007/s12288-017-0862-4. Epub 2017 Aug 21. — View Citation

Gouw SC, van den Berg HM, Oldenburg J, Astermark J, de Groot PG, Margaglione M, Thompson AR, van Heerde W, Boekhorst J, Miller CH, le Cessie S, van der Bom JG. F8 gene mutation type and inhibitor development in patients with severe hemophilia A: systematic review and meta-analysis. Blood. 2012 Mar 22;119(12):2922-34. doi: 10.1182/blood-2011-09-379453. Epub 2012 Jan 26. Review. — View Citation

Hay CR, DiMichele DM; International Immune Tolerance Study. The principal results of the International Immune Tolerance Study: a randomized dose comparison. Blood. 2012 Feb 9;119(6):1335-44. doi: 10.1182/blood-2011-08-369132. Epub 2011 Nov 18. — View Citation

Hay CR, Palmer B, Chalmers E, Liesner R, Maclean R, Rangarajan S, Williams M, Collins PW; United Kingdom Haemophilia Centre Doctors' Organisation (UKHCDO). Incidence of factor VIII inhibitors throughout life in severe hemophilia A in the United Kingdom. Blood. 2011 Jun 9;117(23):6367-70. doi: 10.1182/blood-2010-09-308668. Epub 2011 Apr 6. — View Citation

Miller CH, Platt SJ, Rice AS, Kelly F, Soucie JM; Hemophilia Inhibitor Research Study Investigators. Validation of Nijmegen-Bethesda assay modifications to allow inhibitor measurement during replacement therapy and facilitate inhibitor surveillance. J Thromb Haemost. 2012 Jun;10(6):1055-61. doi: 10.1111/j.1538-7836.2012.04705.x. — View Citation

Peyvandi F, Mannucci PM, Garagiola I, El-Beshlawy A, Elalfy M, Ramanan V, Eshghi P, Hanagavadi S, Varadarajan R, Karimi M, Manglani MV, Ross C, Young G, Seth T, Apte S, Nayak DM, Santagostino E, Mancuso ME, Sandoval Gonzalez AC, Mahlangu JN, Bonanad Boix S, Cerqueira M, Ewing NP, Male C, Owaidah T, Soto Arellano V, Kobrinsky NL, Majumdar S, Perez Garrido R, Sachdeva A, Simpson M, Thomas M, Zanon E, Antmen B, Kavakli K, Manco-Johnson MJ, Martinez M, Marzouka E, Mazzucconi MG, Neme D, Palomo Bravo A, Paredes Aguilera R, Prezotti A, Schmitt K, Wicklund BM, Zulfikar B, Rosendaal FR. A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A. N Engl J Med. 2016 May 26;374(21):2054-64. doi: 10.1056/NEJMoa1516437. — View Citation

Pokras SM, Petrilla AA, Weatherall J, Lee WC. The economics of inpatient on-demand treatment for haemophilia with high-responding inhibitors: a US retrospective data analysis. Haemophilia. 2012 Mar;18(2):284-90. doi: 10.1111/j.1365-2516.2011.02623.x. Epub 2011 Aug 4. — View Citation

Schep SJ, Boes M, Schutgens REG, van Vulpen LFD. An update on the 'danger theory' in inhibitor development in hemophilia A. Expert Rev Hematol. 2019 May;12(5):335-344. doi: 10.1080/17474086.2019.1604213. Epub 2019 Apr 25. — View Citation

Soucie JM, Miller CH, Kelly FM, Payne AB, Creary M, Bockenstedt PL, Kempton CL, Manco-Johnson MJ, Neff AT; Haemophilia Inhibitor Research Study Investigators. A study of prospective surveillance for inhibitors among persons with haemophilia in the United States. Haemophilia. 2014 Mar;20(2):230-7. doi: 10.1111/hae.12302. Epub 2013 Nov 22. — View Citation

Witmer C, Young G. Factor VIII inhibitors in hemophilia A: rationale and latest evidence. Ther Adv Hematol. 2013 Feb;4(1):59-72. doi: 10.1177/2040620712464509. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with inhibitors	Frequency of inhibitors among patients with hemophilia A and B, and VWD	4-days
Primary	Number of patients on demand replacement therapy	Identification of the relationship between on demand replacement therapy and development of factor inhibitors in the study patients	7-days
Primary	Number of participants with low or high responding inhibitors	This would be assessed by of the relationship between inhibitor level and severity of clinical presentation of the patient	7-days