IgIV Plus Prednisone vs High-dose Dexamethasone for ITP

Immune Thrombocytopenia (ITP) Clinical Trial

— IVIORDEX  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04968899
• Other study ID #: APHP200017
• Secondary ID: 2021-000292-37
• Status: Recruiting
• Phase: Phase 3
• Start date: April 7, 2022
• Est. completion date: October 9, 2026

Study information

• Verified date: September 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Matthieu MAHEVAS, MD,PhD
• Phone: +33 (1) 49 81 20 76
• Email: matthieu.mahevas[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 272
• Est. completion date: October 9, 2026
• Est. primary completion date: April 9, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Immune Thrombocytopenia (ITP)
• Purpura, Thrombocytopenic, Idiopathic
• Thrombocytopenia

Intervention

Drug:
• Neofordex®
Oral dexamethasone (Neofordex®) 40 mg (Day1 to Day 4), ± an additional 4-days cycle of dexamethasone between days 10 and 21.
• Intravenous immunoglobulins
IVIg (1g/kg D1-D2) plus oral prednisone (1 mg/kg/day x 21 days (3 weeks))

Locations

Country	Name	City	State
France	Henri Mondor Hospital	Créteil

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to achieve an initial response (R) within 5 days.		5 days
Secondary	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
Secondary	Duration of overall response from Day 1 to the end of the study in the two arms.		Day 1 to 6 months
Secondary	Proportion of early treatment switches across arms		before day 5
Secondary	Number of new bleeding manifestations between Day 1 and Day 5 in the two arms.		between Day 1 and Day 5
Secondary	Rates of response (R) and complete response (CR) in the two arms.		at Day 28 and at 6 months
Secondary	Number of new bleeding manifestations in the two arms.		Between Day 5 and Day 28
Secondary	Number of adverse events in the two arms.		up to 6 months
Secondary	Number of responders in patients with positive and negative anti-platelets antibodies in the two arms.		At 6 months
Secondary	Number of outcome in patients with positive and negative anti-platelets antibodies in the two arms.		At 6 months