Oseltamivir for treatment of thrombocytopenia and plasma leakage in dengue

Treatment Of Thrombocytopenia with Oseltamivir in acute dengue virus infection (TOTO-trial): a randomized, placebo controlled, multicenter trial

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN35227717

Enrollment

Registered

2018-01-12

Start date

2018-01-13

Completion date

Unknown

Last updated

2022-01-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Dengue Infections and Infestations Dengue

Interventions

The study is designed as a phase 2, multicentre, randomized, placebo-controlled, double-blinded intervention trial. Participants will be randomized using block randomization in a 1:1 a

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Admission to hospital 2. Aged 18 years and above; Updated 01/11/2018: Aged 16 years and above 3. Positive result of NS1 rapid test (proven dengue) or positive for acute dengue serology with probable dengue criteria as defined in WHO 2009 criteria 4. Fever <=6 days 5. Platelet count <70 x 10^9/L

Exclusion criteria

Exclusion criteria: 1. Symptoms or signs of another infectious disease 2. Pregnancy or breastfeeding 3. Persistent or recurrent clinical bleeding such as epistaxis, haematemesis, haematochezia, melena, intermenstrual bleeding 4. Chronic liver or kidney disease or active haematological disease 5. Estimated creatinine clearance at moment of enrolment 3x the upper limit of normal 7. Use of platelet function inhibitors or anticoagulants 8. Platelet transfusion during the current hospitalization 9. In patients with earlier platelet count available in past days: platelet number already recovering

Design outcomes

Primary

Measure	Time frame
Current primary outcome measures as of 25/02/2019: 1. Time to platelet recovery (platelet count = 100 x 109/l) is measured using twice daily platelet count measurement from enrollment until discharge or until platelet count = 100 x 109/l 2. Plasma leakage is measured by twice daily haematocrit, daily ultrasonography (looking for gall bladder wall thickness, ascites and pleural fluid) and plasma markers (e.g. Syndecan-1) from enrollment until discharge or until platelet count = 100 x 109/l Previous primary outcome measures: 1. Time to platelet recovery (platelet count = 100 x 109/l) is measured using twice daily platelet count measurement from enrollment until discharge or until platelet count = 100 x 109/l 2. Plasma leakage is measured by twice daily haematocrit and daily ultrasonography (looking for gall bladder wall thickness, ascites and pleural fluid) from enrollment until discharge or until platelet count = 100 x 109/l	—

Measure

Time frame

Current primary outcome measures as of 25/02/2019: 1. Time to platelet recovery (platelet count = 100 x 109/l) is measured using twice daily platelet count measurement from enrollment until discharge or until platelet count = 100 x 109/l 2. Plasma leakage is measured by twice daily haematocrit, daily ultrasonography (looking for gall bladder wall thickness, ascites and pleural fluid) and plasma markers (e.g. Syndecan-1) from enrollment until discharge or until platelet count = 100 x 109/l Previous primary outcome measures: 1. Time to platelet recovery (platelet count = 100 x 109/l) is measured using twice daily platelet count measurement from enrollment until discharge or until platelet count = 100 x 109/l 2. Plasma leakage is measured by twice daily haematocrit and daily ultrasonography (looking for gall bladder wall thickness, ascites and pleural fluid) from enrollment until discharge or until platelet count = 100 x 109/l

—

Secondary

Measure	Time frame
Current secondary outcome measures as of 25/02/2019: 1. Safety of oseltamivir use in dengue is measured using daily measurement of creatinine and liver enzymes from enrollment until discharge or until platelet count =100 x 109/l for a maximum of five days and at week 3 post-enrollment 2. Rate of change of platelet count is measured twice daily using platelet count measurement at 24, 48 and 5 days 3. Number of participants developing severe thrombocytopenia measured using platelet count measurement at enrollment until discharge or until platelet count = 100 x 109/l. 4. Dengue-related complications, especially clinical bleeding is assessed daily using WHO bleeding scores at enrollment until discharge or until platelet count = 100 x 109/l 5. Markers of inflammation, coagulation and endothelial perturbation is measured using daily plasma samples Previous secondary outcome measures: 1. Safety of oseltamivir use in dengue is measured using daily measurement of creatinine and liver enzymes from enrollment until discharge or until platelet count =100 x 109/l for a maximum of five days and at week 3 post-enrollment 2. Rate of change of platelet count is measured twice daily using platelet count measurement at 24, 48 and 5 days 3. Number of participants developing severe thrombocytopenia measured using platelet count measurement at enrollment until discharge or until platelet count = 100 x 109/l. 4. Dengue-related complications, especially clinical bleeding is assessed daily using WHO bleeding scores at enrollment until discharge or until platelet count = 100 x 109/l 5. Flow cytometric platelet studies, including platelet activation and reactivity assays as well as platelet sialic acid expression is measured daily using antibodies against P-selectin and the binding of fibrinogen to platelets in unstimu	—

Measure

Time frame

Current secondary outcome measures as of 25/02/2019: 1. Safety of oseltamivir use in dengue is measured using daily measurement of creatinine and liver enzymes from enrollment until discharge or until platelet count =100 x 109/l for a maximum of five days and at week 3 post-enrollment 2. Rate of change of platelet count is measured twice daily using platelet count measurement at 24, 48 and 5 days 3. Number of participants developing severe thrombocytopenia measured using platelet count measurement at enrollment until discharge or until platelet count = 100 x 109/l. 4. Dengue-related complications, especially clinical bleeding is assessed daily using WHO bleeding scores at enrollment until discharge or until platelet count = 100 x 109/l 5. Markers of inflammation, coagulation and endothelial perturbation is measured using daily plasma samples Previous secondary outcome measures: 1. Safety of oseltamivir use in dengue is measured using daily measurement of creatinine and liver enzymes from enrollment until discharge or until platelet count =100 x 109/l for a maximum of five days and at week 3 post-enrollment 2. Rate of change of platelet count is measured twice daily using platelet count measurement at 24, 48 and 5 days 3. Number of participants developing severe thrombocytopenia measured using platelet count measurement at enrollment until discharge or until platelet count = 100 x 109/l. 4. Dengue-related complications, especially clinical bleeding is assessed daily using WHO bleeding scores at enrollment until discharge or until platelet count = 100 x 109/l 5. Flow cytometric platelet studies, including platelet activation and reactivity assays as well as platelet sialic acid expression is measured daily using antibodies against P-selectin and the binding of fibrinogen to platelets in unstimu

—

Countries

Indonesia

Contacts

Public ContactRahajeng Tunjungputri

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Feb 13, 2026