IgIV Plus Prednisone vs High-dose Dexamethasone for ITP (IVIORDEX)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Immune Thrombocytopenia (ITP)
• Intervention / Treatment: Drug: Neofordex®; Drug: Intravenous immunoglobulins

• Study Type: Interventional
• Enrollment (Estimated): 272
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Matthieu MAHEVAS, MD,PhD; Phone Number: +33 (1) 49 81 20 76; Email: matthieu.mahevas@aphp.fr

Study Locations

• France
  • Créteil, France, 94010
    • Recruiting
    • Henri Mondor Hospital
    • Contact: Matthieu MAHEVAS, PHD; Phone Number: +33149812076; Email: matthieu.mahevas@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2022
• Primary Completion (Estimated): April 9, 2025
• Study Completion (Estimated): October 9, 2026

Study Registration Dates

• First Submitted: July 9, 2021
• First Submitted That Met QC Criteria: July 9, 2021
• First Posted (Actual): July 20, 2021

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 8, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Dexamethasone; Prednisone; Immune thrombocytopenia (ITP); IntraVenous Immunoglobulin
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: APHP200017; 2021-000292-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No