The Comparative Efficacy of Standard Treatment Plus Ribavirin vs Standard Treatment Alone in Preventing Clinically Significant Hemorrhage in Patients With Dengue Fever

NCT06744777 | Completed Phase 3 DMC

• 1 other identifier: KMU/DIR/CTU/2024/012
• Study Type: interventional
• Target: 284
• Locations: 1 country
• Sites: 4

Brief Summary

This study investigates the comparative efficacy of standard treatment plus Ribavirin versus standard treatment alone in preventing clinically significant hemorrhage among patients diagnosed with dengue fever. It is a double-blind, randomized control trial aimed at determining whether the addition of Ribavirin improves clinical outcomes, particularly reducing bleeding events.

Conditions

Dengue Fever; Dengue Hemorrhagic Fever; Severe Dengue

Keywords

Dengue; Hemorrhage; Randomized Controlled Trial; Antiviral Therapy

Outcome Measures

Primary Outcomes (1)

• Prevention of Clinically Significant Hemorrhage

  Evaluate the efficacy of Ribavirin plus standard treatment compared to standard treatment alone in preventing clinically significant hemorrhage (WHO Grade 2 or higher).

  Up to 7 days post-treatment initiation

Secondary Outcomes (5)

• Platelet Count Changes

  At baseline, Day 4, and Day 7 post-treatment initiation.

• Length of Hospital Stay

  From hospital admission to discharge (up to 14 days).

• C-reactive protein

  At baseline, Day 4, and Day 7 post-treatment initiation.

• Serum ferritin

  At baseline, Day 4, and Day 7 post-treatment initiation.

• Lactate dehydrogenase

  At baseline, Day 4, and Day 7 post-treatment initiation.

Other Outcomes (1)

• Adverse Events and Tolerability of Ribavirin

  During the 7-day treatment period and up to 30 days post-treatment follow-up.

Study Arms (2)

Ribavirin + Standard Treatment

EXPERIMENTAL

Participants in this group will receive the standard treatment for dengue fever alongside Ribavirin. Ribavirin will be administered orally at a dose of 15 mg/kg body weight twice daily (BD) for a total duration of 7 days.

Drug: Ribavirin; Other: Standard Treatment

Standard Treatment Alone

ACTIVE COMPARATOR

Participants in this group will receive only the standard treatment for dengue fever, which includes supportive care such as intravenous fluids and platelet transfusions, as required. No additional pharmacological intervention will be provided.

Other: Standard Treatment

Interventions

Ribavirin DRUG

Ribavirin is an antiviral medication administered as part of the intervention arm. It will be provided orally in a dosage of 15 mg/kg body weight twice daily (BD) for a duration of 7 days. The drug has demonstrated efficacy in vitro and in vivo against RNA viruses, including dengue, through mechanisms such as inosine monophosphate inhibition and immunomodulation.

Ribavirin + Standard Treatment

Standard Treatment OTHER

The standard treatment for dengue fever includes supportive care measures aimed at managing symptoms and preventing complications. These measures typically involve: Intravenous (IV) fluid therapy for rehydration and maintaining hemodynamic stability. Platelet transfusion as needed, based on clinical assessment and platelet counts. Antipyretics for fever management (excluding non-steroidal anti-inflammatory drugs to prevent bleeding risks). Continuous monitoring of vital signs and blood parameters, including platelet counts and hematocrit levels. No antiviral drugs or additional pharmacological interventions are included in the standard treatment protocol.

Ribavirin + Standard Treatment; Standard Treatment Alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients aged 18 years and above.
• Hospitalized patients diagnosed with dengue fever, confirmed via:
• Positive Dengue NS1 antigen test
• Dengue IgM antibodies
• Dengue RNA PCR.
• Patients presenting with various severities of illness, as classified by the WHO dengue severity classification.

You may not qualify if:

• Patients taking antiplatelet or anticoagulant medications.
• Patients with known bleeding disorders (e.g., hemophilia, von Willebrand disease, end-stage renal disease, or liver cirrhosis).
• Patients with HIV undergoing antiviral therapy.
• Pregnant women.
• Patients with hypersensitivity to Ribavirin.
• Patients with WHO Grade 1 bleeding (few petechiae without clinical significance).

Sponsors & Collaborators

• Khyber Medical University Peshawar: lead

Study Sites (4)

Lady Reading Hospital

Peshawar, Khyber Pakhtunkhwa, 09152, Pakistan

Location

Gandhara Medical Hospital

Peshawar, Khyber Pakhtunkhwa, Pakistan

Location

Medical Complex Swabi

Swābi, Khyber Pakhtunkhwa, Pakistan

Location

Kohat Institute of Medical Science

Kohat, KPK, Pakistan

Location

Related Publications (7)

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  PMID: 34287274 BACKGROUND

• Roy SK, Bhattacharjee S. Dengue virus: epidemiology, biology, and disease aetiology. Can J Microbiol. 2021 Oct;67(10):687-702. doi: 10.1139/cjm-2020-0572. Epub 2021 Sep 3.

  PMID: 34171205 BACKGROUND

• Sharif N, Sharif N, Khan A, Dey SK. The Epidemiologic and Clinical Characteristics of the 2023 Dengue Outbreak in Bangladesh. Open Forum Infect Dis. 2024 Feb 2;11(2):ofae066. doi: 10.1093/ofid/ofae066. eCollection 2024 Feb.

  PMID: 38390460 BACKGROUND

• Khan U, Azeem S. The rising toll of dengue cases in Pakistan every year: An incipient crisis. Ann Med Surg (Lond). 2022 Mar 31;76:103549. doi: 10.1016/j.amsu.2022.103549. eCollection 2022 Apr. No abstract available.

  PMID: 35495398 BACKGROUND

• Gurugama P, Garg P, Perera J, Wijewickrama A, Seneviratne SL. Dengue viral infections. Indian J Dermatol. 2010;55(1):68-78. doi: 10.4103/0019-5154.60357.

  PMID: 20418983 BACKGROUND

• Tewari K, Tewari VV, Mehta R. Clinical and Hematological Profile of Patients with Dengue Fever at a Tertiary Care Hospital - An Observational Study. Mediterr J Hematol Infect Dis. 2018 Mar 1;10(1):e2018021. doi: 10.4084/MJHID.2018.021. eCollection 2018.

  PMID: 29531658 BACKGROUND

• Ajlan BA, Alafif MM, Alawi MM, Akbar NA, Aldigs EK, Madani TA. Assessment of the new World Health Organization's dengue classification for predicting severity of illness and level of healthcare required. PLoS Negl Trop Dis. 2019 Aug 20;13(8):e0007144. doi: 10.1371/journal.pntd.0007144. eCollection 2019 Aug.

  PMID: 31430283 BACKGROUND

MeSH Terms

Conditions

Dengue; Severe Dengue; Hemorrhage

Interventions

Ribavirin

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Said Amin, MBBS,FCPS

  Department of Medicine Hayatabad Medical Complex Peshawar

  PRINCIPAL INVESTIGATOR

• Sheraz Fazid, MBBS,MPH

  Institute of Public Health and Social Science, Khyber Medical University Peshawar

  PRINCIPAL INVESTIGATOR

• Noman Arif, MBBS

  Institute of Public Health and Social Science, Khyber Medical University Peshawar

  PRINCIPAL INVESTIGATOR

• Akhtar Sherin, MBBS,MHR,PHD

  Kohat Institute of Medical Science Peshawar Pakistan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind methodology, with randomization and treatment assignment concealed.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study employs a parallel group design, where participants are randomly assigned to one of two arms: an intervention group receiving standard treatment plus Ribavirin and a control group receiving standard treatment alone. This approach ensures that each participant is exposed to only one of the two interventions being compared. The study is designed to assess the comparative efficacy of Ribavirin in preventing clinically significant hemorrhage among dengue fever patients while minimizing confounding factors through randomization and blinding.

Study Record Dates

• First Submitted: December 17, 2024
• First Posted: December 20, 2024
• Study Start: December 17, 2024
• Primary Completion: April 28, 2025
• Study Completion: May 29, 2025
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will become available 6 months after the publication of primary results and remain accessible for 5 years.
• Access Criteria: Requests for data sharing will be reviewed by the principal investigator and the ethics committee. Researchers must submit a formal application with a detailed study proposal, including objectives, methodology, and the intended use of the data. A data-sharing agreement will be required to ensure ethical use and data protection compliance.

Locations

PA (4)