IgIV Plus Prednisone vs High-dose Dexamethasone for ITP

NCT04968899 | Recruiting Phase 3 DMC

• 2 other identifiers: APHP2000172021-000292-37
• Study Type: interventional
• Target: 272
• Locations: 1 country
• Sites: 1

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)

Keywords

Immune thrombocytopenia (ITP); Dexamethasone; IntraVenous Immunoglobulin; Prednisone

Outcome Measures

Primary Outcomes (1)

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

  5 days

Secondary Outcomes (9)

• Time to achieve an initial complete response (CR) in the two arms

  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

Study Arms (2)

Experimental group

EXPERIMENTAL

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

Drug: Neofordex®

Control

ACTIVE COMPARATOR

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

Drug: Intravenous immunoglobulins

Interventions

Neofordex® DRUG

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

Also known as: Dexamethasone

Experimental group

Intravenous immunoglobulins DRUG

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

Also known as: Tegeline®, Clayrig®,, Gammagard®,, Octagam®,, Privigen®,, Other IgIV patent medicine

Control

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Henri Mondor Hospital

Créteil, 94010, France

RECRUITING

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

Dexamethasone; Immunoglobulins, Intravenous; Octagam

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Matthieu MAHEVAS, MD,PhD

CONTACT

+33 (1) 49 81 20 76; matthieu.mahevas@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2021
• First Posted: July 20, 2021
• Study Start: April 7, 2022
• Primary Completion: April 9, 2025
• Study Completion (Estimated): October 9, 2026
• Last Updated: September 11, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)