1.
Peri-Operative Eltrombopag or Immune Globulin for Patients with Immune Thrombocytopaenia (The Bridging ITP Trial): Methods and Rationale
Arnold DM, Jamula E, Heddle NM, Cook RJ, Hsia C, Sholzberg M, Lin Y, Kassis J, Blostein M, Larratt L, et al
Thrombosis and haemostasis. 2019
Abstract
BACKGROUND The Bridging ITP Trial is an open-label randomized trial designed to compare the oral thrombopoietin receptor agonist eltrombopag and intravenous immune globulin (IVIG) for patients with immune thrombocytopaenia (ITP) who require an increase in platelet count before elective surgery. Here, we report the study methods and rationale. METHODS We designed a multi-centre, non-inferiority randomized trial comparing daily oral eltrombopag starting 3 weeks pre-operatively, and IVIG administered 1 week pre-operatively for patients with ITP requiring a platelet count increase prior to surgery. Starting dose of eltrombopag is 50 mg daily with a weekly pre-operative dose titration schedule, and treatment is continued for 1 week after surgical haemostasis is achieved. IVIG is administered at a dose of 1 to 2 g/kg 1 week pre-operatively with the allowance for a second dose within 1 week after surgical haemostasis. The objective of the study is to demonstrate non-inferiority of eltrombopag for the primary endpoint of achieving the pre-operative platelet count threshold (50 x 10(9)/L for minor surgery; or 100 x 10(9)/L for major surgery) and sustaining platelet count levels above the threshold for 1 week after surgical haemostasis is achieved, without the use of rescue treatment. Secondary endpoints include thrombosis, bleeding and patient satisfaction. CONCLUSION The Bridging ITP Trial will evaluate the efficacy and safety of eltrombopag as an alternative to IVIG in the peri-operative setting for patients with ITP. The protocol was designed to provide a management strategy that can be applied in clinical practice. CLINICALTRIALS. GOV IDENTIFIER NCT01621204.
2.
Avatrombopag before procedures reduces need for platelet transfusion in patients with chronic liver disease and thrombocytopenia
Terrault N, Chen Y C, Izumi N, Kayali Z, Mitrut P, Tak W Y, Allen L F, Hassanein T
Gastroenterology. 2018;155((3):):705-718
Abstract
BACKGROUND & AIMS Patients with thrombocytopenia and chronic liver disease (CLD) may require platelet transfusions before scheduled procedures to decrease risk of bleeding. We performed 2 randomized, placebo-controlled, phase 3 trials in patients with thrombocytopenia and CLD undergoing scheduled procedures to evaluate the safety and efficacy of avatrombopag in increasing platelet counts in this patient population METHODS In the ADAPT-1 and ADAPT-2 studies, adults with thrombocytopenia and CLD (n=231 and n= 204, respectively) were in 1 of 2 cohorts according to their baseline platelet count (below 40x10(9)/L or 40-50x10(9)/L) and within each cohort randomized (2:1) to 5 daily doses of avatrombopag (60 mg if baseline platelet count below 40x10(9)/L or 40 mg if 40-50x10(9)/L) or placebo. ADAPT-1 was conducted at 75 study sites in 20 countries, from February 2014 through January 2017 and ADAPT-2 was conducted at 74 sites in 16 countries, from December 2013 through January 2017. The primary endpoint was the proportion of patients not requiring platelet transfusions or rescue procedures for bleeding up to 7 days following a scheduled procedure. RESULTS In the ADAPT-1 study, 65.6% of patients who received 60 mg avatrombopag and 88.1% of patients who received 40 mg avatrombopag met the primary endpoint, compared with 22.9% and 38.2% of patients receiving placebo, respectively ((P<.001 for both). In the ADAPT-2 study, 68.6% of patients who received 60 mg avatrombopag and 87.9% of patients who received 40 mg avatrombopag met the primary endpoint compared with 34.9% and 33.3% of patients who received placebo, respectively (P<.001 for both). Avatrombopag led to a measured increase in platelet counts and increased the proportion of patients who achieved the target platelet count ≥ 50x10(9)/L on procedure day vs placebo. The incidence and severity of adverse events were similar for the avatrombopag and placebo groups, and were consistent with those expected in the CLD population. CONCLUSIONS In 2 phase 3 randomized trials, avatrombopag was superior to placebo in reducing the need for platelet transfusions or rescue procedures for bleeding in patients with thrombocytopenia and CLD undergoing a scheduled procedure. ClinicalTrials.gov no: NCT01972529 and NCT01976104.