Background
Phase 3, double-blind, placebo-controlled RCT (CHAMPION). 114 patients (76 eltrombopag, 38 placebo; 2:1 randomization) with chronic idiopathic thrombocytopenic purpura (ITP, duration >6 months), platelet count <30×10⁹/L, and ≥1 prior ITP treatment. Conducted at 63 sites in 23 countries. Eltrombopag is a once-daily oral, small-molecule, non-peptide thrombopoietin receptor agonist (TPO-RA) that binds the transmembrane domain of the TPO receptor (c-Mpl) — a distinct binding site from TPO and romiplostim — stimulating megakaryocyte differentiation and platelet production without activating antibody-mediated platelet destruction.
Interventions and follow up
Arm A: Eltrombopag 50 mg orally once daily × 6 weeks; dose increased to 75 mg/day after 3 weeks if platelet count <50×10⁹/L
Arm B: Placebo orally once daily × 6 weeks on the same schedule; concurrent standard ITP medications were permitted
Primary endpoint: Proportion of patients achieving platelet count ≥50×10⁹/L at day 43
mFollow up: 6 weeks (treatment) + 4-week follow-u
Arm B: Placebo orally once daily × 6 weeks on the same schedule; concurrent standard ITP medications were permitted
Primary endpoint: Proportion of patients achieving platelet count ≥50×10⁹/L at day 43
mFollow up: 6 weeks (treatment) + 4-week follow-u
Results
Response at day 43 (platelet ≥50×10⁹/L): 59% vs 16%, OR 9.61 (95% CI 3.31–27.86), P<.0001
Bleeding reduction (any bleeding at any time): OR 0.49 (95% CI 0.26–0.89), P=.021
Dose escalation to 75 mg (of those eligible): 29% of dose-escalated patients achieved response
Bleeding reduction (any bleeding at any time): OR 0.49 (95% CI 0.26–0.89), P=.021
Dose escalation to 75 mg (of those eligible): 29% of dose-escalated patients achieved response
Adverse events
Main adverse events: Grade 3–4 AEs: 3% (eltrombopag) vs 3% (placebo) — comparable. Treatment discontinuation due to AEs: 4% vs 5% — comparable. Headache and nausea were the most common any-grade AEs. Mild ALT/AST elevations observed. Platelet counts returned to near-baseline within 2 weeks of stopping treatment, consistent with drug's mechanism of action rather than disease remission.
Conclusions
Eltrombopag significantly increased platelet counts to ≥50×10⁹/L and reduced bleeding versus placebo in chronic ITP patients who had failed ≥1 prior therapy, with a tolerability profile similar to placebo, establishing it as an effective oral second-line agent for this condition.
Key Limitations
Key Limitations: Short treatment duration (6 weeks) — the trial established proof of efficacy but did not address durability; platelet counts returned to baseline within 2 weeks of stopping, confirming the drug suppresses thrombocytopenia without inducing disease remission. Sample size relatively small (n=114). No comparison with romiplostim or other TPO-RAs. Liver enzyme monitoring is required; hepatotoxicity risk necessitated boxed warning in early label. Thrombotic events were not observed in this short trial but emerged as a concern in longer-term studies (EXTEND: 6%). Eltrombopag binds to food/dairy (calcium chelation); must be taken 2 hours before or after calcium-rich foods — a common clinical oversight.
Clinical Context
CHAMPION supported FDA approval of eltrombopag (Promacta/Revolade) for chronic ITP in November 2008. Along with romiplostim, eltrombopag is a standard second-line agent after corticosteroids/IVIG fail or cause unacceptable toxicity, and for patients who are not splenectomy candidates or prefer to defer it. Eltrombopag is also approved for severe aplastic anemia (refractory and frontline with horse ATG) and thrombocytopenia in chronic liver disease before procedures. Key difference from romiplostim: oral once-daily vs weekly SC; distinct receptor binding domain; requires ALT monitoring; drug-food interaction with calcium-containing foods.
References
References: Bussel JB et al, Lancet 2009 (CHAMPION primary)