Efficacy of Short Course of Intravenous Dexamethasone and Intravenous Immunoglobulin Therapy in Infection-Related Secondary Hemophagocytic Lymphohistiocytosis (isHLH) (isHLH-IVD/IVIg)

Randomized Controlled Trial to Evaluate and Compare the Efficacy of Short Course of Intravenous Dexamethasone and Intravenous Immunoglobulin Therapy in Infection-Related Secondary Hemophagocytic Lymphohistiocytosis (sHLH)

Rationale/Gaps in Existing Knowledge: Therapy of Infection-associated Secondary Hemophagocytic lymphohistiocytosis (sHLH) in adult lacks evidence from randomized trial guiding first-line immunomodulation and current therapeutic practice primarily extrapolated from decades old pediatric HLH protocols and retrospective studies. In presence of infection very expensive therapy with intravenous Immunoglobulin (IVIG) is preferred over Dexamethasone, however the comparative efficacy of IVIG and Dexamethasone alone remains undefined, especially in resource-constraints settings. (ii) Novelty: This will be among the first randomized controlled trials in adults with infection-associated sHLH, directly comparing efficacy of IVIG with Dexamethasone. The study uniquely integrates clinical outcomes with economic feasibility in a low-middle income setting. (iii) Objectives: Primary objectives will be to compare the efficacy of intravenous (IV) Dexamethasone and IVIG in achieving clinical remission and recovery of HLH-associated cytokines (IL-1, IL-6, TNF-α, IFN-γ, GM-CSF) and Ferritin level. Secondary objectives include assessment of hematologic recovery, adverse events, and short-term mortality. (iv)Method: In this Randomized controlled open-label, non-inferiority clinical trial participants with sHLH, will be allocated (1:1) to receive either short-course of IV Dexamethasone or IVIG along with infection-directed standard care and will be followed-up for 4 weeks to evaluate predefined clinical outcome and laboratory parameters. (v) Expected Outcome: The study aims to establish whether IV Dexamethasone is non-inferior to IVIG for achieving clinical remission, recovery of HLH-associated cytokines level and reduction of short-term mortality. Results are expected to reform evidence-based, cost-effective therapeutic strategies for infection-associated sHLH and improve access to care in resource-constraint healthcare systems.

Study Overview

• Status: Not yet recruiting
• Conditions: Hemophagocytic Lymphohistiocytosis (HLH); Secondary Hemophagocytic Lymphohistiocytosis
• Intervention / Treatment: Drug: Intravenous Immunoglobulin (IVIg) therapy; Drug: Targeted antimicrobial therapy & standard care; Drug: Intravenous Dexamethasone (IVD) therapy

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Deba Prasad Dhibar, MD; Phone Number: +911722756670; Email: drdeba_prasad@yahoo.co.in

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years
• Gender: Male/female
• h-Score probability ≥ 80%
• Known microbiological etiology
• Mild HLH not responding to infection specific targeted antimicrobial therapy (> 72 hours)
• Mild HLH developing new organ dysfunction
• Moderate to severe HLH with life threatening organ dysfunction

Exclusion Criteria:

• Primary (familial) HLH
• Malignancy associated HLH
• HLH associated with autoimmune disease
• EBV associated HLH
• Pregnancy
• Receiving immune modulator therapy within 2 moths
• Participants with HIV
• Consent not given
• Known hypersensitivity to IVIG or Dexamethasone
• Chronic liver disease
• Chronic kidney disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: IVIg; Will receive intravenous Immunoglobulin (IVIg) therapy	Drug: Intravenous Immunoglobulin (IVIg) therapy; Injection IVIg (400 mg/kg Body weight) over an hour IV infusion X 5 days (total cumulative dose 2g/kg).; Drug: Targeted antimicrobial therapy & standard care; Infection specific targeted antimicrobial therapy along with standard medical care
Experimental: IVD; Will receive intravenous Dexamethasone (IVD)	Drug: Targeted antimicrobial therapy & standard care; Infection specific targeted antimicrobial therapy along with standard medical care; Drug: Intravenous Dexamethasone (IVD) therapy; Injection Dexamethasone (10mg/m2) in 100 ml 0.9% normal saline (NS) over half an hour IV infusion X 3 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical remission	Number of participants become persistently asymptomatic without fever for ≥72 hours with h-Score probability <80% and without any HLH-related new organ dysfunction at 1 week and 4 weeks of the IVIG/IVD intervention	4 weeks
The recovery of HLH-associated cytokines	Number of participants having reduction of HLH-associated cytokines (IL-1, IL-6, TNF-α, IFN-γ, GM-CSF) and Ferritin level from the pre-intervention baseline at 1 week and 4 weeks of the IVIG/IVD intervention	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recovery of the hematological parameters	Number of participants with recovery or normalization of the hematological parameters (hemoglobin, total leukocyte count, and platelet count)	4 weeks
Adverse events/ adverse drug reactions	Number of incidence of any adverse events and adverse drug reactions	4 weeks
Duration of hospital stay	Number of days of hospital admission	4 weeks
Incidence of relapse of HLH: Recurrence of HLH after achieving clinical remission	Number of participants having recurrence of HLH after achieving clinical remission	4 weeks

Collaborators and Investigators

• Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh
• Collaborators: Indian Council of Medical Research
• Investigators: Principal Investigator: Deba Prasad Dhibar, MD, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Study record dates

Study Major Dates

• Study Start (Estimated): October 15, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2029

Study Registration Dates

• First Submitted: October 1, 2026
• First Submitted That Met QC Criteria: October 1, 2026
• First Posted (Actual): October 6, 2026

Study Record Updates

• Last Update Posted (Actual): October 6, 2026
• Last Update Submitted That Met QC Criteria: October 1, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Keywords: Dexamethasone; Hemophagocytic lymphohistiocytosis (HLH); Intravenous Immunoglobulin (IVIg); Infection associated secondary HLH (isHLH)
• Additional Relevant MeSH Terms: Lymphatic Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Hemic and Lymphatic Diseases; Lymphohistiocytosis, Hemophagocytic; Health Services Administration; Health Care Quality, Access, and Evaluation; Amino Acids, Peptides, and Proteins; Proteins; Quality of Health Care; Quality Indicators, Health Care; Enzymes; Enzymes and Coenzymes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Immunoglobulin G; Oxidoreductases Acting on CH-CH Group Donors; Oxidoreductases; Immunoglobulins, Intravenous; Standard of Care; Therapeutics; Isovaleryl-CoA Dehydrogenase
• Other Study ID Numbers: PGI/IEC/2026/SPL-1447

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

All the reasonable data requests should be submitted to the principal investigator (DPD) for consideration.

Drug and device information, study documents

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