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.
Age ≥ 18 years
Gender: Male/female
h-Score probability ≥ 80%
Known microbiological etiology
Primary (familial) HLH
Malignancy associated HLH
HLH associated with autoimmune disease
EBV associated HLH
Parallel
Intravenous Immunoglobulin (IVIg) therapy
DrugInjection IVIg (400 mg/kg Body weight) over an hour IV infusion X 5 days (total cumulative dose 2g/kg).
Intravenous Dexamethasone (IVD) therapy
DrugInjection Dexamethasone (10mg/m2) in 100 ml 0.9% normal saline (NS) over half an hour IV infusion X 3 days
Targeted antimicrobial therapy & standard care
DrugInfection specific targeted antimicrobial therapy along with standard medical care
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
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
Recovery of the hematological parameters
Number of participants with recovery or normalization of the hematological parameters (hemoglobin, total leukocyte count, and platelet count)
Adverse events/ adverse drug reactions
Number of incidence of any adverse events and adverse drug reactions
Duration of hospital stay
Number of days of hospital admission
Incidence of relapse of HLH: Recurrence of HLH after achieving clinical remission
Number of participants having recurrence of HLH after achieving clinical remission
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Post Graduate Institute of Medical Education and Research, Chandigarh
Lead sponsor
Indian Council of Medical Research
Collaborator
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