IgIV Plus Prednisone vs High-dose Dexamethasone for ITP

Study Overview
=================
Brief Summary
-----------------
ITP patients with low platelet count and active bleeding symptoms are at risk of life-threatening bleeding and therefore require a treatment with a rapid effect, reliable, and sustained. The combination of intravenous immunoglobulin (IVIg) and prednisone (1 mg/kg per day), is more rapidly and more frequently effective than high dose methylprednisolone to increase the platelet count. This combination is therefore usually given in patients with platelets count < 20 x 109/L and moderate to severe bleeding manifestations. Based on common practice in France and on French ITP guidelines, on average 50 % of patients with ITP and profound thrombocytopenia do actually receive IVIg (mostly during the initial phase of the disease) corresponding to approximately 1,500 ITP patients per year in France. Whereas IVIg is usually well tolerated, renal insufficiency and congestive heart failure may occur, moreover IVIg are costly and non-easily available with supply difficulties in many countries including France. High dose dexamethasone (DXM) (ie: 40 mg/d for 4 days) has recently emerged as a promising treatment for ITP. One recent meta-analysis as well as a controlled prospective trial suggest that the initial overall response was higher (> 80 %) and the time to response was shorter with dexamethasone (DXM) 40 mg/d given for 4 days compared to standard prednisone. The investigators hypothesize that DXM could be a reasonable non-inferior alternative to IVIg, more convenient for patients with less adverse events and economically cost-effective for patients with moderate and severe bleeding manifestations.

Official Title
-----------------
Intravenous Immunoglobulin Plus Oral Prednisone or High-dose Dexamethasone, for Adults With Immune Thrombocytopenia (ITP) With Moderate and Severe Bleeding: a Randomized, Multicentre Trial

Conditions
-----------------
Immune Thrombocytopenia (ITP)

Intervention / Treatment
-----------------
* Drug: Neofordex®
* Drug: Intravenous immunoglobulins


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years ≤ 80 years Diagnosis of ITP whatever the duration of the disease (newly diagnosed or relapsed) according to the standard definition Platelet count ≤ 20 x 109/L Any cutaneous and/or any mucosal bleeding manifestations Affiliated to a social security regime Written consent from patient Exclusion Criteria: Symptomatic COVID-19 disease Life-threatening bleeding defined as Intracranial hemorrhage and/or active organ bleeding (GI tract, urinary tract or menorrhagia with at least a 2 g/dl decrease of hemoglobin value from baseline). Ongoing anticoagulation treatment (Therapeutic Low molecular weight heparins (LMWHs), direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs)) Previous non-response to IVIg or DEX Treatment with prednisone (1 mg/kg per day) for more than 3 days Any, contraindications to the prescribed Ig IV or prednisone patent medicine and to Neofordex® Ongoing severe infection Severe Renal insufficiency (DFG < 45 ml.min.1.73m2) Severe Cardiac insufficiency (FEVG < 30 %) Ongoing viral infection (uncontrolled HIV, Viral hepatitis, herpes, varicella, zona). Uncontrolled diabetes (Acido-cetosis) Psychotic state not yet controlled by treatment Inability or refusal to understand or refusal to sign the informed consent from study participation Persons deprived of their liberty by judicial or administrative decision, Persons under legal protection (guardianship, curatorship) Pregnant or breastfeeding woman or ineffective contraception Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Oral dexamethasone (Neofordex®) 40 mg (Day1 to Day 4), ± an additional 4-days cycle of dexamethasone between days 10 and 21 | Drug: Neofordex®<br>* Oral dexamethasone (Neofordex®) 40 mg (Day1 to Day 4), ± an additional 4-days cycle of dexamethasone between days 10 and 21.<br>* Other names: Dexamethasone;|
| Active Comparator: Control<br>IVIg (1g/kg D1-D2) plus prednisone (1 mg/kg/day x 21 days (3 weeks)) | Drug: Intravenous immunoglobulins<br>* IVIg (1g/kg D1-D2) plus oral prednisone (1 mg/kg/day x 21 days (3 weeks))<br>* Other names: Other IgIV patent medicine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to achieve an initial response (R) within 5 days. |  | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to achieve an initial complete response (CR) in the two arms | complete response (CR): defined by a platelet count > 100 x 109/L in the absence use of any other ITP directed therapies between Day 1 and Day 5 | between Day 1 and Day 5 | 
| Duration of overall response from Day 1 to the end of the study in the two arms. |  | Day 1 to 6 months | 
| Proportion of early treatment switches across arms |  | before day 5 | 
| Number of new bleeding manifestations between Day 1 and Day 5 in the two arms. |  | between Day 1 and Day 5 | 
| Rates of response (R) and complete response (CR) in the two arms. |  | at Day 28 and at 6 months | 
| Number of new bleeding manifestations in the two arms. |  | Between Day 5 and Day 28 | 
| Number of adverse events in the two arms. |  | up to 6 months | 
| Number of responders in patients with positive and negative anti-platelets antibodies in the two arms. |  | At 6 months | 
| Number of outcome in patients with positive and negative anti-platelets antibodies in the two arms. |  | At 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immune thrombocytopenia (ITP), Dexamethasone, IntraVenous Immunoglobulin, Prednisone