Adult Dengue Platelet Study

Study Overview
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Brief Summary
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Retrospective data in children with dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), and in adults with dengue fever (DF), suggested a lack of benefit from prophylactic platelet transfusion for severe thrombocytopenia in dengue patients without bleeding. However, in Taiwan and Singapore, platelet transfusion was given to 13-50% of hospitalised dengue patients. This is a prospective randomised study to examine the safety and efficacy of prophylactic platelet transfusion in adults with dengue and severe thrombocytopenia without bleeding. The hypotheses are: Prophylactic platelet transfusion is safe in hospitalised dengue patients with severe thrombocytopenia. Prophylactic platelet transfusion is effective in preventing bleeding in hospitalised dengue patients with severe thrombocytopenia.

Detailed Description
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Patients fulfilling inclusion and exclusion criteria, and giving informed consent, will be randomised to a treatment arm of 4 units of platelets for every day they have a platelet count <20x10^3/uL, or a control arm with supportive care. Patients will be followed up daily till hospital discharge, and again at day 21. It is assumed that the incidence of bleeding from randomization to Day 7 or discharge, whichever earlier, is 10% for the control (no transfusion) group and 5% for the intervention (transfusion) group. With 1:1 allocation ratio, to attain 80% power and one-sided 5% type I error rate, the required number of subjects in each arm is 382 by a Chi-square test with Yates' continuity correction. If a drop-out rate of 5% is allowed, the required number increases to approximately 400 per arm.

Official Title
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Adult Dengue Platelet Study

Conditions
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Dengue Fever

Intervention / Treatment
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* Procedure: Platelet transfusion
* Other: Supportive care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 21years Probable or confirmed dengue a) Confirmed dengue: laboratory confirmation of acute dengue by either i) positive polymerase chain reaction (PCR) for viral ribonucleic acid (RNA), or ii)positive NS1 antigen test with a compatible clinical syndrome b) Probable dengue: Positive acute dengue serology and clinical presentation fulfilling either WHO 1997 or 2009 criteria for probable dengue. i) 1997 criteria: Acute febrile illness and two or more of the following: headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, leucopoenia ii) 2009 criteria: Fever and two of the following: nausea/vomiting, rash, aches/pains, positive tourniquet test, leucopoenia, one or more warning sign abdominal pain/tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleed, lethargy/restlessness, liver enlargement >2cm, increase in haematocrit concurrent with rapid decrease in platelet count Platelets ≤ 20x103/μL

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Platelet transfusion<br>4 units of platelets for patients with platelet count <20x10^3/uL | Procedure: Platelet transfusion<br>* 4 units of platelets for patients with platelet count <20x10^3/uL<br>|
| Other: Supportive care<br>No platelet transfusion for patients with platelet count <20x10^3/uL | Other: Supportive care<br>* Supportive care includes symptomatic treatment, fluid therapy and monitoring of full blood count and blood pressure<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical bleeding excluding petechiae with a subgroup analysis for severe clinical bleeding. |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet increment post-transfusion |  | 5 years | 
| Time to platelet > 50 x 10^3/uL |  | 5 years | 
| Changes in cytokines |  | 5 years | 
| Length of stay |  | 5 years | 
| Plasma leakage |  | 5 years | 
| DHF/DSS |  | 5 years | 
| ICU admission |  | 5 years | 
| Death |  | 5 years | 
| Secondary bacterial infection |  | 5 years | 
| Adverse events from transfusion |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dengue, Platelet transfusion, Bleeding, Prevention