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

The Comparative Efficacy of Standard Treatment Plus Ribavirin vs Standard Treatment Alone in Preventing Clinically Significant Hemorrhage in Patients With Dengue Fever: A Double-blind, Randomized Control Trial

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.

Study Overview

• Status: Completed
• Conditions: Dengue Fever; Dengue Hemorrhagic Fever; Severe Dengue
• Intervention / Treatment: Drug: Ribavirin; Other: Standard Treatment

Detailed Description

Dengue fever, a significant public health concern, presents varying severity from asymptomatic to life-threatening complications such as hemorrhage or shock. This study evaluates the effectiveness of Ribavirin when combined with standard treatment in mitigating severe bleeding complications in dengue patients. Conducted at multiple public sector hospitals in Khyber Pakhtunkhwa, the trial employs a rigorous methodology, including block randomization, double-blinding, and predefined eligibility criteria. Outcomes include changes in bleeding grades, platelet counts, acute-phase reactants, and hospital stay length. The findings aim to inform policy decisions and enhance dengue fever management protocols.

• Study Type: Interventional
• Enrollment (Actual): 284
• Phase: Phase 3

Contacts and Locations

Study Locations

• Pakistan
  • KPK
    • Kohat, KPK, Pakistan
      • Kohat Institute of Medical Science
  • Khyber Pakhtunkhwa
    • Peshawar, Khyber Pakhtunkhwa, Pakistan, 09152
      • Lady Reading Hospital
    • Peshawar, Khyber Pakhtunkhwa, Pakistan
      • Gandhara Medical Hospital
    • Swābi, Khyber Pakhtunkhwa, Pakistan
      • Medical Complex Swabi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ribavirin + Standard Treatment; 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; 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.; Other: Standard Treatment; 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.
Active Comparator: Standard Treatment Alone; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Hospital Stay	Evaluate and compare the duration of hospitalization in the intervention and control groups.	From hospital admission to discharge (up to 14 days).
Platelet Count Changes	Compare levels of platelets count between the intervention and control groups.	At baseline, Day 4, and Day 7 post-treatment initiation.
C-reactive protein	Compare the C-reactive protein in between intervention and control group	At baseline, Day 4, and Day 7 post-treatment initiation.
Serum ferritin	Compare the serum ferritin in between intervention and control group	At baseline, Day 4, and Day 7 post-treatment initiation.
Lactate dehydrogenase	Compare levels of lactate dehydrogenase between the intervention and control groups.	At baseline, Day 4, and Day 7 post-treatment initiation.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events and Tolerability of Ribavirin	Document adverse events, including side effects, and assess the tolerability of Ribavirin in the intervention group.	During the 7-day treatment period and up to 30 days post-treatment follow-up.

Collaborators and Investigators

• Sponsor: Khyber Medical University Peshawar
• Investigators: Principal Investigator: 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

Publications and helpful links

General Publications

• Gutierrez E, Sanchez I, Diaz O, Valles A, Balderrama R, Fuentes J, Lara B, Olimon C, Ruiz V, Rodriguez J, Bayardo LH, Chan M, Villafuerte CJ, Padayachee J, Sun A. Current Evidence for Stereotactic Body Radiotherapy in Lung Metastases. Curr Oncol. 2021 Jul 15;28(4):2560-2578. doi: 10.3390/curroncol28040233.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2024
• Primary Completion (Actual): April 28, 2025
• Study Completion (Actual): May 29, 2025

Study Registration Dates

• First Submitted: December 17, 2024
• First Submitted That Met QC Criteria: December 17, 2024
• First Posted (Actual): December 20, 2024

Study Record Updates

• Last Update Posted (Actual): June 26, 2025
• Last Update Submitted That Met QC Criteria: June 23, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Dengue; Hemorrhage; Antiviral Therapy
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Wounds and Injuries; Pathologic Processes; Infections; RNA Virus Infections; Virus Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Body Temperature Changes; Heat Stress Disorders; Hyperthermia; Dengue; Hemorrhage; Fever; Hemorrhagic Fevers, Viral; Severe Dengue; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Antiviral Agents; Ribavirin
• Other Study ID Numbers: KMU/DIR/CTU/2024/012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified individual participant data (IPD) will be made available to other researchers upon request. This includes data related to demographic information, baseline clinical characteristics, treatment interventions, and outcome measures. Personal identifiers will be removed to ensure participant confidentiality.
• IPD Sharing Time Frame: Data will become available 6 months after the publication of primary results and remain accessible for 5 years.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No