Clinical trial NCT01030211: Adult Dengue Platelet Study
Official title: Adult Dengue Platelet Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dengue Fever
Keywords: Dengue
Platelet transfusion
Bleeding
Prevention
Lead sponsor: Tan Tock Seng Hospital
Sponsor class: OTHER
Collaborators: name: Singapore General Hospital
name: Changi General Hospital
name: National University Hospital, Singapore
name: University of Malaya
First posted: 2009-12-11
Enrollment: 372
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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:

1. Prophylactic platelet transfusion is safe in hospitalised dengue patients with severe thrombocytopenia.
2. Prophylactic platelet transfusion is effective in preventing bleeding in hospitalised dengue patients with severe thrombocytopenia.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 21years
2. 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
3. Platelets ≤ 20x103/μL

Primary outcomes:
measure: Clinical bleeding excluding petechiae with a subgroup analysis for severe clinical bleeding.
timeFrame: 5 years
Secondary outcomes:
measure: Platelet increment post-transfusion
timeFrame: 5 years
measure: Time to platelet > 50 x 10^3/uL
timeFrame: 5 years
measure: Changes in cytokines
timeFrame: 5 years
measure: Length of stay
timeFrame: 5 years
measure: Plasma leakage
timeFrame: 5 years
measure: DHF/DSS
timeFrame: 5 years
measure: ICU admission
timeFrame: 5 years
measure: Death
timeFrame: 5 years
measure: Secondary bacterial infection
timeFrame: 5 years
measure: Adverse events from transfusion
timeFrame: 5 years
Other outcomes:
Locations:
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital, National University Health System, Singapore General Hospital, Changi General Hospital
Study officials:
affiliation: Tan Tock Seng Hospital
name: Yee S Leo, FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Archuleta S, Chia PY, Wei Y, Syed-Omar SF, Low JG, Oh HM, Fisher D, Ponnampalavanar SSL, Wijaya L, Kamarulzaman A, Lum LCS, Tambyah PA, Leo YS, Lye DC. Predictors and Clinical Outcomes of Poor Platelet Recovery in Adult Dengue With Thrombocytopenia: A Multicenter, Prospective Study. Clin Infect Dis. 2020 Jul 11;71(2):383-389. doi: 10.1093/cid/ciz850.
citation: Lye DC, Archuleta S, Syed-Omar SF, Low JG, Oh HM, Wei Y, Fisher D, Ponnampalavanar SSL, Wijaya L, Lee LK, Ooi EE, Kamarulzaman A, Lum LC, Tambyah PA, Leo YS. Prophylactic platelet transfusion plus supportive care versus supportive care alone in adults with dengue and thrombocytopenia: a multicentre, open-label, randomised, superiority trial. Lancet. 2017 Apr 22;389(10079):1611-1618. doi: 10.1016/S0140-6736(17)30269-6. Epub 2017 Mar 8.
citation: Tomashek KM, Biggerstaff BJ, Ramos MM, Perez-Guerra CL, Garcia Rivera EJ, Sun W. Physician survey to determine how dengue is diagnosed, treated and reported in puerto rico. PLoS Negl Trop Dis. 2014 Oct 9;8(10):e3192. doi: 10.1371/journal.pntd.0003192. eCollection 2014 Oct.