Newly Diagnosed Immune Thrombocytopenia Testing the Standard Steroid Treatment Against Combined Steroid & Mycophenolate

NCT03156452 | Completed Phase 3 DMC

• 3 other identifiers: ON/2016/60042017-001171-23PB-PG-0815-20016
• Study Type: interventional
• Target: 123
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study of two treatment pathways \[Standard steroid treatment versus combined steroid and Mycophenolate (MMF)\] for subjects with newly diagnosed Immune Thrombocytopenia (ITP). ITP is an illness that causes bruising and bleeding due to a low platelet count (blood cells essential for normal clotting). Patients are first given high dose steroids but most suffer side effects (e.g. difficulty sleeping, weight gain, moods swings, high blood pressure and diabetes). In addition, the majority of patients become ill again when the steroids are stopped - only about 20% stay well long term. ITP is relatively rare, non-cancerous in nature and the rare impact on survival of ITP have prevented it from being a priority for research funding, with first line treatment being unsatisfactory and unchallenged for decades. This underestimates the profound adverse impact an ITP diagnosis and its treatment has on individual patients, many of whom are young. MMF is often used as the next stage treatment for ITP and it works well. However, it can take up to 2 months to work during which patients continue to be at risk of bleeding, bruising, fatigue and usually need more steroids which they find intolerable. They are required to come to hospital for weekly blood tests and for many this impacts on work. We want to find out whether it would benefit more patients if everyone takes MMF at diagnosis instead of current practice (waiting for the illness to come back). We plan to test this by comparing the current way we treat patients to a new way with patients given MMF right at the start of their treatment. 120 patients from 20 different hospitals will be asked to take part and half will be randomly chosen for the new pathway.

Conditions

Immune Thrombocytopenia

Outcome Measures

Primary Outcomes (1)

• Time from randomisation to treatment failure.

  To include patients who are refractory (platelet count \<30x109/L in spite of 2 weeks treatment in the steroid arm or platelet count \<30x109/L in spite of 2 months treatment in the steroid +MMF arm) or who initially respond but then relapse (defined clinically as platelet count \<30x109/L and need for further therapy).

  1 year

Secondary Outcomes (12)

• Medication side effects, toxicity and other adverse events (including infection episodes)

  Up to 12 months post randomisation

• Bleeding events

  up to 12 months post randomisation

• Remission rates

  Up to 12 months post randomisation

• Time to relapse and time to next therapy

  Up to 12 months post randomisation

• Cumulative cortiocosteroid dose

  Up to 12 months post randomisation

Study Arms (2)

Steroid & Mycophenolate mofetil 1st line

EXPERIMENTAL

Mycophenolate mofetil: 1 gm bd Non-IMP Steroid: 1mg/kg od 4 days (maximum of 100mg), 40mg od 2 weeks, 20mg od 2 weeks, 10mg od 2 weeks, 5mg od 2 weeks then 5mg alternate days 2 weeks.

Drug: Mycophenolate Mofetil

Prednisolone (Steroid) alone 1st line

ACTIVE COMPARATOR

Non-IMP steroid: 1mg/kg od 4 days (maximum of 100mg), 40mg od 2 weeks, 20mg od 2 weeks, 10mg od 2 weeks, 5mg od 2 weeks then 5mg alternate days 2 weeks.

Drug: Prednisolone

Interventions

Mycophenolate Mofetil DRUG

500 mg and 250mg tablets for oral administration

Steroid & Mycophenolate mofetil 1st line

Prednisolone DRUG

5mg tablets for oral administration

Also known as: Steroid

Prednisolone (Steroid) alone 1st line

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients (males and females) \>16 years old with a diagnosis of ITP, a pl count \<30x109/L AND a clinical need for first line treatment.
• Patients have provided written informed consent

You may not qualify if:

• Patients with HIV, Hepatitis B or C, or Common Variable immunodeficiency.
• Women of child bearing potential require a pregnancy test result within 7 days prior to randomisation (as per 7.1 below) to rule out unintended pregnancy
• Contraindications to MMF or steroid (see SPC, Appendix 2) including patients with hypersensitivity to mycophenolate mofetil, mycophenolic acid or to any of the excipients or active significant infection
• Patients not capable of giving informed consent (e.g. due to incapacity)
• Patients unwilling to follow contraceptive advice if allocated to MMF treatment arm.

Sponsors & Collaborators

• University Hospitals Bristol and Weston NHS Foundation Trust: lead
• Cardiff University: collaborator

Study Sites (1)

University Hospital Bristol NHS Foundation Trust

Bristol, BS2 8ED, United Kingdom

Location

Related Publications (3)

• Stimpson ML, Wolf J, Charbit B, Williams EL, Lait PJP, Schewitz-Bowers LP, Lee RWJ, Bradbury CA. Systemic immunosuppression depletes peripheral blood regulatory B cells in patients with immune thrombocytopenia. Br J Haematol. 2024 Feb;204(2):644-648. doi: 10.1111/bjh.19144. Epub 2023 Oct 12.

  PMID: 37823469 DERIVED

• Bradbury CA, Pell J, Hill Q, Bagot C, Cooper N, Ingram J, Breheny K, Kandiyali R, Rayment R, Evans G, Talks K, Thomas I, Greenwood R. Mycophenolate Mofetil for First-Line Treatment of Immune Thrombocytopenia. N Engl J Med. 2021 Sep 2;385(10):885-895. doi: 10.1056/NEJMoa2100596.

  PMID: 34469646 DERIVED

• Pell J, Greenwood R, Ingram J, Wale K, Thomas I, Kandiyali R, Mumford A, Dick A, Bagot C, Cooper N, Hill Q, Bradbury CA. Trial protocol: a multicentre randomised trial of first-line treatment pathways for newly diagnosed immune thrombocytopenia: standard steroid treatment versus combined steroid and mycophenolate. The FLIGHT trial. BMJ Open. 2018 Oct 18;8(10):e024427. doi: 10.1136/bmjopen-2018-024427.

  PMID: 30341143 DERIVED

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

Mycophenolic Acid; Prednisolone; Steroids

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)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Pregnadienetriols; Pregnadienes; Pregnanes; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Charlotte Bradbury

  University of Bristol

  STUDY DIRECTOR

Study Design

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

Model Details: A multicentre, open label randomised clinical trial of MMF with steroid as a first line treatment for patients with ITP against the standard care pathway involving steroids alone as first line treatment.

Study Record Dates

• First Submitted: May 2, 2017
• First Posted: May 17, 2017
• Study Start: October 25, 2017
• Primary Completion: March 5, 2020
• Study Completion: March 5, 2020
• Last Updated: October 26, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)