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

NCT ID: NCT03939637

Last Updated: 2025-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 122 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-02
• Study Completion Date: 2025-02-26

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.

Detailed Description

This is a prospective, open label, randomized, two-arm, multi-center Phase 3 trial.

Patients with newly diagnosed ITP are randomized 2:1 to receive the experimental treatment, eltrombopag, or investigator's choice of 3 standard therapies. The primary objective is to determine if the proportion of patients with platelet response is significantly greater in patients treated with eltrombopag compared to those treated with standard therapies.

Conditions

Immune Thrombocytopenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Eltrombopag

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

Group Type: EXPERIMENTAL

Eltrombopag

Intervention Type: 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.

Standard first-line therapy

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)

Group Type: ACTIVE_COMPARATOR

Steroids

Intervention Type: DRUG

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

IVIG

Intervention Type: DRUG

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

Rho(D) Immune Globulin

Intervention Type: DRUG

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

Interventions

Eltrombopag

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.

Intervention Type: DRUG

Steroids

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

Intervention Type: DRUG

IVIG

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

Intervention Type: DRUG

Rho(D) Immune Globulin

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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:

1. Upfront treatment: Patient within 10 days of ITP diagnosis who has not received previous treatment OR

2. 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

Exclusion Criteria

• 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
• Impaired cardiac function, such as:

• Known prolonged QTc, with corrected QTc >450 msec
• Other clinically significant cardio-vascular disease (e.g., uncontrolled hypertension, history of labile hypertension),
• History of known structural abnormalities (e.g. cardiomyopathy).
• History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following:

• Recent myocardial infarction (within last 6 months),
• Uncontrolled congestive heart failure,
• Unstable angina (within last 6 months),
• Clinically significant (symptomatic) cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third degree AV block without a pacemaker.)
• Long QT syndrome, family history of idiopathic sudden death, congenital long QT syndrome or additional risk factors for cardiac repolarization abnormality, as determined by the investigator.
• Known immediate or delayed hypersensitivity reaction to eltrombopag or its excipient.
• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study. Women of childbearing potential (have achieved menarche) must have a negative serum or urine pregnancy test and agree to use basic methods of contraception (if sexually active) or maintain abstinence for the duration of the study. Basic contraception methods include:

• Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
• Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject
• Barrier methods of contraception: Condom or Occlusive cap. For the UK: with spermicidal foam/gel/film/cream/ vaginal suppository
• Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
• Male patients who are sexually active and do not agree to abstinence or to use a condom during intercourse while taking eltrombopag, and for 7 days after stopping treatment.
• History of alcohol/drug abuse
• Presence of a medical condition that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
• Concurrent participation in an investigational study within 30 days prior to enrollment or within 5-half-lives of the investigational product, whichever is longer. Note: parallel enrollment in a non-therapeutic trial such as disease registry or biology study is permitted.

Other Eligibility Criteria Considerations All patients and/or their parents or legal guardians must sign a written informed consent (and assent when applicable)

• Patients and/or parents who are unable to read at a grade 2 level will be excluded from the patient-reported outcome component of the study, as will non-English speaking patients and/or parents when there is no availability of translated versions in their spoken language . They will not be excluded from all other aspects of the study

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boston Children's Hospital

OTHER

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: collaborator

Baylor College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Amanda Grimes

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amanda Grimes, MD

Role: PRINCIPAL_INVESTIGATOR

Baylor College of Medicine - Texas Children's Hospital

Locations

Children's of Alabama

Birmingham, Alabama, United States

Phoenix CHildren's Hospital

Phoenix, Arizona, United States

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Children's Hospital of Orange County

Orange, California, United States

UCSF Benioff Children's Hospital

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Children's National Medical Center

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

University of Florida College of Medicine

Gainesville, Florida, United States

Alfac Cancer and Blood Disorder Center: Scottish Rite

Atlanta, Georgia, United States

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

Chicago, Illinois, United States

Riley Hospital for Children-Indiana University

Indianapolis, Indiana, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Children's Hospital and Clinics of Minnesota

Minneapolis, Minnesota, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Columbia University Irving Medical Center

New York, New York, United States

Weill Cornell Medical College

New York, New York, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Randall Children's Hospital

Portland, Oregon, United States

Oregon Health and Science University

Portland, Oregon, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Hasbro Children's Hospital

Providence, Rhode Island, United States

St. Jude Children's Hospital

Memphis, Tennessee, United States

Texas Children's Hospital

Houston, Texas, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

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 Oct 22. doi: 10.1001/jama.2025.18168. Online ahead of print.

Reference Type: DERIVED

PMID: 41123939 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34452956 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CETB115JUS33T

Identifier Type: OTHER

Identifier Source: secondary_id

ICON 3

Identifier Type: OTHER

Identifier Source: secondary_id

H-42131 ICON 3

Identifier Type: -

Identifier Source: org_study_id