IgIV Plus Prednisone vs High-dose Dexamethasone for ITP

NCT ID: NCT04968899

Last Updated: 2023-09-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 272 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-04-07
• Study Completion Date: 2026-10-09

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.

Conditions

Immune Thrombocytopenia (ITP)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental group

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

Group Type: EXPERIMENTAL

Neofordex®

Intervention Type: DRUG

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

Control

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

Group Type: ACTIVE_COMPARATOR

Intravenous immunoglobulins

Intervention Type: DRUG

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

Interventions

Neofordex®

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

Intervention Type: DRUG

Intravenous immunoglobulins

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

Intervention Type: DRUG

Other Intervention Names

Dexamethasone; Tegeline®; Clayrig®,; Gammagard®,; Octagam®,; Privigen®,; Other IgIV patent medicine

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Henri Mondor Hospital

Créteil, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Matthieu MAHEVAS, MD,PhD

Role: CONTACT

matthieu.mahevas@aphp.fr

+33 (1) 49 81 20 76

Facility Contacts

Matthieu MAHEVAS, PHD

Role: primary

matthieu.mahevas@aphp.fr

+33149812076

Other Identifiers

2021-000292-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

APHP200017

Identifier Type: -

Identifier Source: org_study_id