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

Primary Purpose

Immune Thrombocytopenia (ITP)

Status

Recruiting

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

Neofordex®

Intravenous immunoglobulins

About this trial

This is an interventional treatment trial for Immune Thrombocytopenia (ITP) focused on measuring Immune thrombocytopenia (ITP), Dexamethasone, IntraVenous Immunoglobulin, Prednisone

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Henri Mondor HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Experimental group

Control

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Duration of overall response from Day 1 to the end of the study in the two arms.

Proportion of early treatment switches across arms

Number of new bleeding manifestations between Day 1 and Day 5 in the two arms.

Rates of response (R) and complete response (CR) in the two arms.

Number of new bleeding manifestations in the two arms.

Number of adverse events in the two arms.

Number of responders in patients with positive and negative anti-platelets antibodies in the two arms.

Number of outcome in patients with positive and negative anti-platelets antibodies in the two arms.

Full Information

NCT ID

NCT04968899

First Posted

July 9, 2021

Last Updated

September 8, 2023

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT04968899

Brief Title

IgIV Plus Prednisone vs High-dose Dexamethasone for ITP

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 7, 2022 (Actual)

Primary Completion Date

April 9, 2025 (Anticipated)

Study Completion Date

October 9, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Immune Thrombocytopenia (ITP)

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

272 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Experimental group

Arm Type

Experimental

Arm Description

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

Arm Title

Control

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Neofordex®

Other Intervention Name(s)

Dexamethasone

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Intravenous immunoglobulins

Other Intervention Name(s)

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

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Time Frame

5 days

Secondary Outcome Measure Information:

Title

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

Description

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

Time Frame

between Day 1 and Day 5

Title

Duration of overall response from Day 1 to the end of the study in the two arms.

Time Frame

Day 1 to 6 months

Title

Proportion of early treatment switches across arms

Time Frame

before day 5

Title

Number of new bleeding manifestations between Day 1 and Day 5 in the two arms.

Time Frame

between Day 1 and Day 5

Title

Rates of response (R) and complete response (CR) in the two arms.

Time Frame

at Day 28 and at 6 months

Title

Number of new bleeding manifestations in the two arms.

Time Frame

Between Day 5 and Day 28

Title

Number of adverse events in the two arms.

Time Frame

up to 6 months

Title

Number of responders in patients with positive and negative anti-platelets antibodies in the two arms.

Time Frame

At 6 months

Title

Number of outcome in patients with positive and negative anti-platelets antibodies in the two arms.

Time Frame

At 6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Matthieu MAHEVAS, MD,PhD

Phone

+33 (1) 49 81 20 76

matthieu.mahevas@aphp.fr

Facility Information:

Facility Name

Henri Mondor Hospital

City

Créteil

ZIP/Postal Code

94010

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Matthieu MAHEVAS, PHD

Phone

+33149812076

matthieu.mahevas@aphp.fr

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION

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IgIV Plus Prednisone vs High-dose Dexamethasone for ITP

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