1.
Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study
Bussel JB de Miguel PG, Despotovic JM, Grainger JD, Sevilla J, Blanchette VS, Krishnamurti L, Connor P, David M, Boayue KB, Matthews DC, et al
The Lancet Haematology. 2015;2((8)):e315-25.
Abstract
BACKGROUND The oral thrombopoietin receptor agonist eltrombopag is approved for treatment of adults with chronic immune thrombocytopenia. In the PETIT trial, we aimed to investigate the efficacy and safety of eltrombopag in children with persistent or chronic immune thrombocytopenia. METHODS PETIT was a three-part, randomised, multicentre, placebo-controlled study done at 22 centres in the USA, UK, Canada, Spain, France, and the Netherlands. Patients aged 1-17 years with immune thrombocytopenia lasting for 6 months or longer and platelets less than 30 x 10(9) per L who had received at least one previous treatment were enrolled. We enrolled patients into three cohorts consisting of patients aged 12-17, 6-11, and 1-5 years. We established patients' starting doses with an open-label, dose-finding phase with five patients in each cohort. During the dose-finding phase, patients aged 6-17 years started eltrombopag at 25 mg once per day (125 mg for those weighing <27 kg) and patients aged 1-5 years received 07 mg/kg per day to a maximum of 2 mg/kg unless otherwise approved. We permitted dose adjustments on the basis of platelet response up to a maximum dosage of 75 mg per day. Additional patients were then recruited and randomly assigned (2:1) to receive either eltrombopag or placebo tablets (or oral suspension formulation if aged 1-5 years) once per day for 7 weeks at the previously established doses. Starting doses for the double-blind phase were 375 mg/day for patients aged 12-17 years; 50 mg/day for patients weighing 27 kg or more (25 mg for east Asian patients) and 25 mg/day for patients weighing less than 27 kg (125 mg once per day for east Asian patients) for patients aged 6-11 years; and 15 mg/kg once per day (08 mg/kg once per day for east Asian patients) for patients aged 1-5 years. Randomisation was done by the GlaxoSmithKline Registration/Medication Ordering System and both patients and study personnel were masked to treatment assignments. Patients who completed treatment were then enrolled into an open-label phase and all patients could receive up to 24 weeks of eltrombopag. The primary outcome was the proportion of patients achieving a platelet count of 50 x 10(9) per L or more at least once from weeks 1-6 (days 8 to 43) of the randomised phase of the study in the absence of rescue therapy. We assessed efficacy in the intent-to-treat population, which consisted of all patients assigned to treatment, and we assessed safety in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT00908037. FINDINGS Between Oct 2, 2009, and June 22, 2011, we recruited 15 patients, with five patients in each age cohort, into the open-label dose-finding phase who did not progress into the double-blind phase. From March 17, 2010, to Jan 15, 2013, we randomly assigned 67 patients to treatment, with 45 patients assigned to receive eltrombopag (16 children aged 12-17 years, 19 aged 6-11 years, and ten aged 1-5 years) and 22 to receive placebo (eight children aged 12-17 years, nine aged 6-11 years, and five aged 1-5 years). However, two patients assigned to receive eltrombopag did not receive the study drug and one was lost to follow-up, and one patient assigned to receive placebo was given eltrombopag. From weeks 1 to 6, 28 (62%) patients who received eltrombopag, compared with seven (32%) who received placebo, achieved the primary endpoint of platelet count 50 x 10(9) per L or more at least once without rescue (odds ratio 431, 95% CI 139-1334, p=0011). The most common adverse events with eltrombopag were headache (13 [30%] patients receiving eltrombopag vs nine [43%] patients receiving placebo), upper respiratory tract infection (11 [25%] patients vs two [10%] patients), and diarrhoea (seven [16%] patients vs one [5%] patient). Grade 3 or 4 adverse events occurred in five (11%) patients receiving eltrombopag and four (19%) patients receiving placebo, and serious adverse events (four [9%] patients receiving eltrombopag and two (10%) patients receiving placebo) w
2.
Eltrombopag treatment of childhood persistent and chronic immune thrombocytopenia: final results of the PETIT study (TRA108062), a phase 2, placebo-controlled clinical trial
Bussel JB, Garcia de Miguel P, Despotovic J, Grainger JD, Sevilla Navarro J, Blanchette V, Connor P, David M, Matthews D, Marcello L, et al
Haematologica. 2014;99((S1):):263.. Abstract No. S733.
3.
A trial of desmopressin to reduce blood loss in patients undergoing spinal fusion for idiopathic scoliosis
Guay J, Reinberg C, Poitras B, David M, Mathews S, Lortie L, Rivard GE
Anesthesia & Analgesia. 1992;75((3):):405-10.
Abstract
Desmopressin (DDAVP) has been reported to reduce bleeding in patients undergoing spinal fusion. To evaluate its efficacy in normal patients, 30 healthy young patients (ASA physical status I or II) undergoing spinal fusion for idiopathic scoliosis were randomly allocated to receive either 100 mL of physiologic saline solution (placebo group) or DDAVP (10 micrograms/m2 of body surface area) (DDAVP group) in a prospective, double-blind trial. Intraoperative blood loss was measured by weighing sponges and suction drainage and postoperative bleeding by wound drainage. The amount of blood loss expressed as a percent of the estimated blood volume was similar in both groups during the intraoperative period (67.0% +/- 28.8% [mean +/- SD] placebo group vs 57.4% +/- 26.5% DDAVP group), the postoperative period up to 24 h (32.5% +/- 6.4% placebo group vs 31.1% +/- 10.6% DDAVP group), and both periods (94.3% +/- 29.4% placebo group vs 88.2% +/- 30.7% DDAVP group). With the dose used in our study, we conclude that DDAVP does not reduce surgical bleeding in patients undergoing spinal fusion for idiopathic scoliosis.