Intravenous Immunoglobulin plus oral prednisone or high-dose dexamethasone, for adults with immune thrombocytopenia (ITP) with moderate and severe bleeding: a randomized, multicentre trial (IVIORDEX).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

7 Apr 2022 → ongoing

Decision date (initial)

2024-11-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

DGOS - French Ministry of Health

External identifiers

EU CT number

2024-516403-16-00

EudraCT number

2021-000292-37

ClinicalTrials.gov

NCT04968899

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To demonstrate the non-inferiority in term of short-term response of oral dexamethasone given at 40 mg on days 1 to 4 compared to IVIg given at 1g/kg on days 1 and 2 in combination with prednisone (1 mg/kg per day for 3 weeks) in adult patients with immune thrombocytopenia (ITP) with mild to severe bleeding manifestations.

Secondary objectives 10

1. To compare initial rate of CR in the two arms and the delay to obtain a CR.
2. To compare the duration of the response in the two arms.
3. To assess the acceptability/feasibility of the protocol, by comparing the proportion of early treatment switches (before day 5) across arms.
4. To estimate the interaction between treatment effect and the severity/risk of bleeding.
5. To compare the initial response on bleeding manifestations in both arms.
6. To compare the duration of hospital, stay in the two arms.
7. To compare the efficacy (overall response rate) at Day 28 and 6 months in the two arms.
8. To compare safety profile in the two arms.
9. To estimate the incremental (decremental) cost effectiveness of DXM vs IVIg at 6 months given the non-inferiority design our hypothesis is that DMX is cheaper and non-inferior decrementally cost effective compared to IVIg.
10. To assess whether the presence of anti-platelet antibodies is associated with the outcome (Chronic or Cured) at 6 months in the two arms.

Conditions and MedDRA coding

Adult patients with immune thrombocytopenia (ITP) with mild to severe bleeding manifestations

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥ 18 years ≤ 80 years
2. Diagnosis of ITP whatever the duration of the disease (newly diagnosed or relapsed) according to the standard definition
3. Platelet count ≤ 20 x 109/L
4. Any cutaneous and/or any mucosal bleeding manifestations
5. Affiliated to a social security regime
6. Written consent from patient

Exclusion criteria 17

1. Symptomatic COVID-19 disease
2. 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).
3. Ongoing anticoagulation treatment (Therapeutic Low molecular weight heparins (LMWHs), direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs))
4. Previous non-response to IVIg or DEX
5. Treatment with prednisone (1 mg/kg per day) for more than 3 days
6. Any contraindications to the prescribed Ig IV or prednisone patent medicine and to Neofordex®
7. Ongoing severe infection
8. Severe Renal insufficiency (DFG < 45 ml.min.1.73m2)
9. Severe Cardiac insufficiency (FEVG < 30 %)
10. Ongoing viral infection (uncontrolled HIV, Viral hepatitis, herpes, varicella, zona)
11. Uncontrolled diabetes (Acido-cetosis)
12. Psychotic state not yet controlled by treatment
13. Inability or refusal to understand or refusal to sign the informed consent from study participation
14. Persons deprived of their liberty by judicial or administrative decision
15. Persons under legal protection (guardianship, curatorship)
16. Pregnant or breastfeeding woman or ineffective contraception
17. Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time (in days) to achieve an initial response (R) within 5 days. - Initial response (R) will be defined according to international guidelines (5) as a platelet count ≥ 30x109/L with at least a doubling of the baseline value in the absence of new bleeding and absence of the use of any other ITP directed therapies (other than the one of the treatment arm)

Secondary endpoints 10

1. Time (in days) to achieve an initial complete response (CR) in both arms (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) in the two arms.
2. Duration in time (in days) of overall response from Day 1 to the end of the study (6 months) in the two arms.
3. Proportion of early (before day 5) treatment switches across arms
4. Number of new bleeding manifestations between Day 1 and Day 5 in two arms. Bleeding manifestations will be assessed the score reported by Khellaf et al. without taking into account the age of the patient.
5. Rates of response (R) and complete response (CR) at 28 days, and 6 months in the two arms.
6. Number of bleeding manifestations between Day 5 and Day 28 in the two arms.
7. Number of days of hospitalization between Day 1 and Day 28 in the two arms.
8. Number of adverse events in the two arms.
9. Incremental (decremental) cost effectiveness ratio expressed in cost per responder at 6 months
10. Comparison of the number of responders, and outcome at 6 months in patients with positive and negative anti-platelets antibodies in the two arms.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Matthieu Mahévas

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Matthieu Mahévas

Locations

1 EU/EEA country · 38 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications