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Effect of Aspirin, Hemodilution and Desmopressin on Platelet Dysfunction

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ClinicalTrials.gov Identifier: NCT01382134
Recruitment Status : Completed
First Posted : June 27, 2011
Last Update Posted : November 15, 2013
Sponsor:
Information provided by (Responsible Party):
Tsui Pui Yee, The University of Hong Kong

Tracking Information
First Submitted Date  ICMJE June 23, 2011
First Posted Date  ICMJE June 27, 2011
Last Update Posted Date November 15, 2013
Study Start Date  ICMJE July 2011
Actual Primary Completion Date July 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 23, 2011)
Platelet function [ Time Frame: Day 6 after aspirin intake ]
Venous blood sample will be taken from subjects before and after injection of DDAVP. Blood sample will be subjected to: (i) complete blood count, (ii) PFA-100 platelet function analyzer, (iii) fibrinogen, and (iv) vWF:Ag concentration for analysis.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01382134 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Aspirin, Hemodilution and Desmopressin on Platelet Dysfunction
Official Title  ICMJE Effect of Aspirin, in Vitro Hemodilution and Desmopressin on Platelet Dysfunction Associated With Mild Hypothermia in Healthy Volunteers
Brief Summary

Study hypothesis: Desmopressin (DDAVP) can improve platelet function under influence of aspirin, hemodilution and mild hypothermia

Mild hypothermia (34-35oC) is known to cause platelet dysfunction. This could lead to increased surgical bleeding and increased transfusion requirement during surgery. Although this hypothermia-induced platelet dysfunction seems to be reversible with warming, this is not always possible or desirable.

Desmopressin (DDAVP) is a drug which has proven efficacy in improving platelet function in uraemic and cirrhosis patients, and in reducing blood loss in selected surgeries. In a recent study, we have found that subcutaneous injection of 1.5 mcg (1/10th the usual dose) is already sufficient to fully reverse the platelet dysfunction seen at 32oC. We have demonstrated in another study that prolongation of the bleeding time in a 20% hemodiluted sample predicts increased postoperative bleeding after total knee replacement.

We have therefore designed this study as a follow up to our last two studies on DDAVP and hypothermia, to investigate whether hemodilution affects hypothermia induced platelet dysfunction and the response to DDAVP. In addition, another common cause of perioperative platelet dysfunction is the intake of COX inhibitors, particularly aspirin by patients. Therefor the effect of aspirin on hypothermia induced platelet dysfunction and the response to DDAVP, will also be investigated.

Detailed Description

Mild hypothermia (34-35oC) is known to cause platelet dysfunction. Increased surgical bleeding and increased transfusion requirement at this temperature range has been reported in both cardiac and noncardiac surgeries. This degree of hypothermia is common during any general anaesthesia, particularly during surgeries which invlove major fluid shift and large area exposure of patients, e.g. trauma and burn patients.

Although this hypothermia-induced platelet dysfunction seems to be reversible with warming, warming is not always possible or desirable. During major trauma or burn surgery, surface warming of patient is practically difficult. During surgeries with major blood loss and fluid shift, heat loss usually occurs at a rate that is more rapid than any warming device can catch up with. During neurosurgery, cooling may be beneficial to neurological outcome.

Desmopressin (DDAVP) is a drug which has proven efficacy in improving platelet function in uraemic and cirrhosis patients, and in reducing blood loss in selected surgeries. In a previous in vitro study, we have found that desmopressin significantly improves platelet function at 32oC. The improvement is seen with a very low concentration of desmopressin in vitro, which suggests that probably doses much smaller than the "standard dose" (15 mcg slow iv or subcutaneous) may be useful. In keeping with this in vitro study, in a more recent study, we have found that subcutaneous injection of 1.5 mcg (1/10th the usual dose) is already sufficient to fully reverse the platelet dysfunction seen at 32oC.

One of the limitations of our previous two studies is that the degree of platelet dysfuction observed at 32oC is relatively mild, with only around 20% prolongation of the closure times on the PFA-100® platelet function analyser. The clinical significance of such prolongation remains uncertain. However, we have demonstrated previously in another study that prolongation of the closure time to >188 sec in a 20% hemodiluted sample predicts increased postoperative bleeding after total knee replacement. We have therefore designed this study as a follow up to our last two studies on DDAVP and hypothermia, to investigate whether hemodilution affects hypothermia induced platelet dysfunction and the response to DDAVP.

In addition, another common cause of perioperative platelet dysfunction is the intake of COX inhibitors, particularly aspirin by patients. Therefor the effect of aspirin on hypothermia induced platelet dysfunction and the response to DDAVP, will also be investigated.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Platelet Dysfunction
  • Hemodilution
  • Mild Hypothermia
  • NSAID
  • Desmopressin
Intervention  ICMJE
  • Drug: Aspirin, desmopressin
    Aspirin 100mg daily for 3 days Desmopressin 15 microgram subcutaneously once only
  • Drug: Placebo, desmopressin
    Placebo 1 tab daily for 3 days Desmopressin 15 microgram subcutaneously once only
Study Arms  ICMJE
  • Placebo Comparator: Placebo group
    Subjects will be given placebo daily for 3 days. On day 4 an early morning urine sample will be collected for detection of aspirin metabolite (11-dehydro thromboxane B2). On day 6 venous blood sample will be collected, 17mls before and 17 mls after injection of DDAVP 15 microgram subcutaneously. The blood samples will then be subjected for platelet function analysis.
    Intervention: Drug: Placebo, desmopressin
  • Active Comparator: Aspirin group
    Subjects will be given aspirin 100mg daily for 3 days. On day 4 an early morning urine sample will be collected for detection of aspirin metabolite (11-dehydro thromboxane B2). On day 6 venous blood sample will be collected, 17mls before and 17 mls after injection of DDAVP 15microgram subcutaneously. The blood samples will then be subjected for platelet function analysis.
    Intervention: Drug: Aspirin, desmopressin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 23, 2011)
60
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2013
Actual Primary Completion Date July 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 60 adult Chinese subjects aged 18-60 without known platelet disorder, thrombocytopenia, history of taking drugs that may affect platelet function including herbal preparations.

Exclusion Criteria:

  1. Any known platelet or coagulation disorder
  2. Expected surgical operation or dental treatment within one week of scheduled drug intake.
  3. Known peptic ulcer disease
  4. Obesity (BMI >=30)
  5. Pregnant or lactating women.
  6. Known chronic liver or renal disease.
  7. Coronary artery, carotid artery or peripheral artery disease
  8. Recent history of taking antiplatelet drugs, anticoagulants or herbal preparations.
  9. Smoker or alcohol user
  10. Mentally incapable of providing informed consent
  11. Students or junior staff members who had direct working relationship with the PI
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01382134
Other Study ID Numbers  ICMJE UW 11-075
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tsui Pui Yee, The University of Hong Kong
Study Sponsor  ICMJE The University of Hong Kong
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account The University of Hong Kong
Verification Date November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP