Eltrombopag vs Standard Front Line Management for Newly Diagnosed Immune Thrombocytopenia (ITP) in Children

NCT03939637 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: H-42131 ICON 3CETB115JUS33TICON 3
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 27

Brief Summary

This is an investigator initiated, multicenter, open label, randomized phase 3 study for subjects with newly diagnosed ITP from ages 1 to less than 18 years old.

Conditions

Immune Thrombocytopenia

Keywords

ITP; Immune Thrombocytopenia; Newly Diagnosed Immune Thrombocytopenia; Newly Diagnosed ITP

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients With a Platelet Response

  To determine if the percentage of patients with a platelet response is significantly greater in patients with newly diagnosed ITP treated with eltrombopag than those treated with standard first-line treatments

  12 weeks

Secondary Outcomes (11)

• Bleeding Score

  1 year

• Cumulative Number of Rescue Therapies Required

  12 weeks

• Platelet Response Among Patients Requiring Rescue Therapy During Weeks 1-2 of Study

  12 weeks

• Need for Treatment

  6 months

• Treatment Response

  1 year

Other Outcomes (10)

• Time to Response

  1 year

• Platelet-specific Endpoints

  1 year

• Time to Platelet Count

  1 year

Study Arms (2)

Eltrombopag

EXPERIMENTAL

Patients randomized to eltrombopag will be treated for 12 weeks, with the possibility to continue therapy for up to 1 year depending on response.

Drug: Eltrombopag

Standard first-line therapy

ACTIVE COMPARATOR

Subjects randomized to the standard therapy arm will receive one of three treatments at the discretion of the treating physician. Patients who previously failed standard management prior to study entry must be treated with a different agent than their original failed agent. e.g. Patient who failed steroids could receive either IVIg or anti-D if randomized to the standard treatment arm. Standard therapy will be administered as commercially available drug. Investigator may choose amongst the following: * IVIg: IVIG 1 g/kg x1 (no steroids for pre-medication or adjunctive therapy) * Steroids: Prednisone/Prednisolone 4 mg/kg/day (Max 120 mg/day) x 4 days * Rho(D) Immune Globulin: Anti-D globulin 75 mcg/kg x1 (no steroids for pre-medication or adjunctive therapy)

Drug: Steroids; Drug: IVIG; Drug: Rho(D) Immune Globulin

Interventions

Eltrombopag DRUG

Starting dose for eltrombopag will be based on manufacturer recommendations, and drug will be titrated to effect per guidelines. * Children 1 to 5 years: Initial: 25 mg once daily * Children ≥6 years and Adolescents: Initial: 50 mg once daily (25 mg once daily for patients of East-Asian ethnicity \[e.g., Chinese, Japanese, Korean, Taiwanese\]) Dose should be titrated based on platelet response. Maximum dose: 75 mg once daily.

Eltrombopag

Steroids DRUG

Prednisone/Prednisolone 4mg/kg/day (Max 120 mg/day) x 4 day

Standard first-line therapy

IVIG DRUG

IVIG 1 g/kg x1 (no steroids for pre-medication or adjunctive therapy)

Standard first-line therapy

Rho(D) Immune Globulin DRUG

Anti-D globulin 75 mcg/kg x1 (no steroids for pre-medication or adjunctive therapy)

Standard first-line therapy

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: 1- \<18 years
• Newly diagnosed ITP (\<3 months from diagnosis (first abnormal platelet count), per international working group definition17)
• Platelets \<30 x 10\^9/L at screening
• Requires pharmacologic treatment from the perspective of the treating clinician.
• Need to treat is at the discretion of the investigator, but there should be clinical equipoise about the use of eltrombopag vs standard treatment options (patients should not, in the opinion of the investigator, require concomitant therapy at time of enrollment).
• Treatment options include one of three standard therapies, (IVIg, steroids, or Anti-D). For example, if patient has previously shown no response to IVIg or steroids and is Rh-negative, patient would not be eligible for study.
• Patient population includes both:
• Upfront treatment: Patient within 10 days of ITP diagnosis who has not received previous treatment OR
• Treatment failure: Patients who have failed standard management (observation or treatment with one or more first-line agents)
• Failure of observation: no platelet recovery (\>30 x 10\^9/L) with observation \>10 days from diagnosis, with need to treat
• Poor response to first-line agent (platelets remain \<30 x10\^9/L)
• Initial response to first-line agent, but response wanes and platelets fall below 30 x10\^9/L
• Family willing and able to return for required lab studies

You may not qualify if:

• Severe bleeding: Buchanan Overall Grade 4 or 5 bleeding, or severe bleeding requiring emergent treatment at the discretion of the provider. (e.g., intracranial hemorrhage, pulmonary hemorrhage, bleeding with ongoing need for pRBC transfusion)
• Prior treatment with TPO-RA (eltrombopag or romiplostim)
• Known secondary ITP (due to lupus, CVID, ALPS)
• Known HIV (or history of HIV positivity) or Hepatitis C (screening not required if no clinical suspicion)
• Evans Syndrome: positive direct Coombs with evidence of active hemolysis (elevated lactate dehydrogenase (LDH) or reticulocyte count not attributable to recent treatment or bleeding)
• Any Malignancy
• History of stem cell transplant or solid organ transplant
• aspartate aminotransferase (AST) or ALT \>2 x upper limit of normal (ULN)
• Total bilirubin \>1.5 × ULN
• Subjects with liver cirrhosis (as determined by the investigator)
• Creatinine \>2.5 × ULN
• Known active or uncontrolled infections not responding to appropriate therapy
• On anticoagulation or anti-platelet agents
• Known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator.
• Baseline ophthalmic problems that may potentiate cataract development

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Boston Children's Hospital: collaborator
• University of California, San Francisco: collaborator

Study Sites (27)

Children's of Alabama

Birmingham, Alabama, 35233, United States

Location

Phoenix CHildren's Hospital

Phoenix, Arizona, 85016, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

UCSF Benioff Children's Hospital

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

Alfac Cancer and Blood Disorder Center: Scottish Rite

Atlanta, Georgia, 30342, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Riley Hospital for Children-Indiana University

Indianapolis, Indiana, 46202, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Hospital and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Randall Children's Hospital

Portland, Oregon, 97227, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Hasbro Children's Hospital

Providence, Rhode Island, 02903, United States

Location

St. Jude Children's Hospital

Memphis, Tennessee, 38105, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (2)

• Shimano KA, Grimes AB, Kaicker S, Shah SJ, Gunn E, Bhat RV, Kochhar M, Rothman JA, Rose MJ, Briones M, Nakano TA, Lebensburger JD, Lambert MP, Fritch Lilla SA, Jesudas R, Lee-Miller CA, Thompson AA, Rifkin-Zenenberg S, Majumdar S, Crary SE, Hege K, Ford JB, Bies JJ, Fort J, Wynn TT, Hsieh L, Ruiz ME, Dinu B, Wong JMW, Kao PC, Kim TO, Arnold SD, Bennett CM, Despotovic JM, Klaassen RJ, Neufeld EJ, Neunert CE, London WB, Grace RF. Eltrombopag for Newly Diagnosed Pediatric Immune Thrombocytopenia Requiring Treatment: The PINES Randomized Clinical Trial. JAMA. 2025 Nov 25;334(20):1816-1826. doi: 10.1001/jama.2025.18168.

  PMID: 41123939 DERIVED

• Shimano KA, Grace RF, Despotovic JM, Neufeld EJ, Klaassen RJ, Bennett CM, Ma C, London WB, Neunert C. Phase 3 randomised trial of eltrombopag versus standard first-line pharmacological management for newly diagnosed immune thrombocytopaenia (ITP) in children: study protocol. BMJ Open. 2021 Aug 27;11(8):e044885. doi: 10.1136/bmjopen-2020-044885.

  PMID: 34452956 DERIVED

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

eltrombopag; Steroids; Immunoglobulins, Intravenous; Rho(D) Immune Globulin

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)

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

Results Point of Contact

• Title: Amanda Grimes
• Organization: Baylor College of Medicine/ Texas Children's Hospital

abgrimes@texaschildrens.org

832-822-4217

Study Officials

• Amanda Grimes, MD

  Baylor College of Medicine - Texas Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 25, 2019
• First Posted: May 7, 2019
• Study Start: May 2, 2019
• Primary Completion: April 17, 2024
• Study Completion: February 26, 2025
• Last Updated: July 29, 2025
• Results First Posted: July 29, 2025

Record last verified: 2025-07

Locations

US (27)