IVIORDEX: IgIV Plus Prednisone vs High-dose Dexamethasone for ITP

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04968899

Collaborator

(none)

272

Enrollment

Arms

54.1

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Immune Thrombocytopenia (ITP)	Drug: Neofordex® Drug: Intravenous immunoglobulins	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

272 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Jan 5, 2025

Anticipated Study Completion Date :

Jul 5, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental group Oral dexamethasone (Neofordex®) 40 mg (Day1 to Day 4), ± an additional 4-days cycle of dexamethasone between days 10 and 21	Drug: Neofordex® Oral dexamethasone (Neofordex®) 40 mg (Day1 to Day 4), ± an additional 4-days cycle of dexamethasone between days 10 and 21. Other Names: Dexamethasone
Active Comparator: Control IVIg (1g/kg D1-D2) plus prednisone (1 mg/kg/day x 21 days (3 weeks))	Drug: Intravenous immunoglobulins IVIg (1g/kg D1-D2) plus oral prednisone (1 mg/kg/day x 21 days (3 weeks)) Other Names: Tegeline® Clayrig®, Gammagard®, Octagam®, Privigen®, Other IgIV patent medicine

Arm

Intervention/Treatment

Experimental: Experimental group

Oral dexamethasone (Neofordex®) 40 mg (Day1 to Day 4), ± an additional 4-days cycle of dexamethasone between days 10 and 21

Drug: Neofordex®

Oral dexamethasone (Neofordex®) 40 mg (Day1 to Day 4), ± an additional 4-days cycle of dexamethasone between days 10 and 21.

Other Names:

Dexamethasone

Active Comparator: Control

IVIg (1g/kg D1-D2) plus prednisone (1 mg/kg/day x 21 days (3 weeks))

Drug: Intravenous immunoglobulins

IVIg (1g/kg D1-D2) plus oral prednisone (1 mg/kg/day x 21 days (3 weeks))

Other Names:

Tegeline®

Clayrig®,

Gammagard®,

Octagam®,

Privigen®,

Other IgIV patent medicine

Outcome Measures

Primary Outcome Measures

Time to achieve an initial response (R) within 5 days. [5 days]

Secondary Outcome Measures

Time to achieve an initial complete response (CR) in the two arms [between Day 1 and Day 5]
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
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years ≤ 80years
Diagnosis of ITP whatever the duration, 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:

PCR SARS-CoV2 positive
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 (HIV, Viral hepatitis, herpes, varicella, zona).
Uncontrolled diabetes
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.