Prevention of Bleeding in Patient With Cirrhosis Undergoing Dental Extraction

Liver Cirrhosis Clinical Trial

Official title:

Intranasal DDAVP in Preventing Bleeding During Dental Extraction in Cirrhotic Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00816127
• Other study ID #: 02-0727
• Status: Completed
• Phase: N/A
• First received: December 29, 2008
• Last updated: December 31, 2008
• Start date: October 2003
• Est. completion date: May 2007

Study information

• Verified date: December 2008
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate how effective and cost saving 1-deamino-8-D-arginine vasopressin (desmopressin, DDAVP) is as opposed to the transfusion of blood products in preventing bleeding after teeth extraction in persons with severe liver disease being evaluated for liver transplant.

Description:

Liver cirrhosis is associated with dysregulation of the coagulation system resulting in an increased bleeding tendency in cirrhotic patients. The treatment approach to offset these abnormalities may involve transfusion with fresh frozen plasma (FFP) and platelets. Fluid overload may become a concern as the large amount of FFP (10-20mls/kg or >1,500ml) required to achieve the hemostatic effect could be contraindicated in some patients. Furthermore, repeated platelet transfusion induces alloimmunization and refractoriness to new transfusion, which is an important issue in patients on the waiting list for liver transplantation in which HLA-matched and cross-matched platelets may be required. Non-transfusional drugs that help to stop bleeding have been used in patients with congenital bleeding disorders. 1-deamino-8-D-arginine vasopressin (DDAVP, Desmopressin), a synthetic analogue of the antidiuretic hormone, L-arginine, has been used as a non-transfusional form of replacement therapy in a variety of congenital and acquired bleeding disorders. Through unknown mechanisms, DDAVP shortens the prolonged bleeding times of cirrhotic patients despite the high plasma concentrations of Factor VIII and von Willebrand factor sound in chronic liver disease, indicating that it might be useful as a prophylactic treatment in cirrhotic patients undergoing minimally invasive procedures, i.e. dental extraction.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: May 2007
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• adult patients with biopsy-proven liver cirrhosis or clinical/radiological evidence of cirrhosis, requiring dental extraction

• platelet count of 30,000-50,000/microL and/or INR 2.0-3.0

Exclusion Criteria:

• the presence of other bleeding disorders besides cirrhosis such as renal dysfunction (creatinine > 2.0) or HIV

• receipt of blood transfusion within 2 weeks prior to study

• recent acute decompensation of liver cirrhosis

• malignancy excluding hepatocellular carcinoma in the absence of portal vein thrombosis

• treatment with anti-platelet medications (aspirin, non-steroidal anti-inflammatory drugs or clopidogrel) within ten days prior to the extraction

• documented allergy to DDAVP.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Coagulopathy
• Hemostatic Disorders
• Liver Cirrhosis

Intervention

Drug:
• Desmopressin
intranasal desmopressin (300µg)

Biological:
• blood transfusion
fresh frozen plasma 10ml/kg and/or 1 unit of single donor platelets

Locations

Country	Name	City	State
United States	Mount Sinai School of Medicine	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai

Country where clinical trial is conducted

United States, 

References & Publications (7)

Amitrano L, Guardascione MA, Brancaccio V, Balzano A. Coagulation disorders in liver disease. Semin Liver Dis. 2002 Feb;22(1):83-96. Review. — View Citation

de la Fuente B, Kasper CK, Rickles FR, Hoyer LW. Response of patients with mild and moderate hemophilia A and von Willebrand's disease to treatment with desmopressin. Ann Intern Med. 1985 Jul;103(1):6-14. — View Citation

Kobrinsky NL, Israels ED, Gerrard JM, Cheang MS, Watson CM, Bishop AJ, Schroeder ML. Shortening of bleeding time by 1-deamino-8-D-arginine vasopressin in various bleeding disorders. Lancet. 1984 May 26;1(8387):1145-8. — View Citation

Mannucci PM, Remuzzi G, Pusineri F, Lombardi R, Valsecchi C, Mecca G, Zimmerman TS. Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia. N Engl J Med. 1983 Jan 6;308(1):8-12. — View Citation

Mannucci PM, Ruggeri ZM, Pareti FI, Capitanio A. 1-Deamino-8-d-arginine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrands' diseases. Lancet. 1977 Apr 23;1(8017):869-72. — View Citation

Mannucci PM. Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood. 1997 Oct 1;90(7):2515-21. Review. — View Citation

Saulnier J, Marey A, Horellou MH, Goudemand J, Lepoutre F, Donazzan M, Gazengel C, Torchet M, Letang C, Schuhmann C, et al. Evaluation of desmopressin for dental extractions in patients with hemostatic disorders. Oral Surg Oral Med Oral Pathol. 1994 Jan;77(1):6-12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Necessity of rescue blood transfusion in patients who received DDAVP or blood transfusion prior to dental extraction.		48 hours	No