1.
Perioperative oral eltrombopag versus intravenous immunoglobulin in patients with immune thrombocytopenia: a non-inferiority, multicentre, randomised trial
Arnold DM, Heddle NM, Cook RJ, Hsia C, Blostein M, Jamula E, Sholzberg M, Lin Y, Kassis J, Larratt L, et al
The Lancet. Haematology. 2020;7(9):e640-e648
Abstract
BACKGROUND Patients with immune thrombocytopenia are at risk of bleeding during surgery, and intravenous immunoglobulin is commonly used to increase the platelet count. We aimed to establish whether perioperative eltrombopag was non-inferior to intravenous immunoglobulin. METHODS We did a randomised, open-label trial in eight academic hospitals in Canada. Patients were aged at least 18 years, with primary or secondary immune thrombocytopenia and platelet counts less than 100 × 10(9) cells per L before major surgery or less than 50 × 10(9) cells per L before minor surgery. Previous intravenous immunoglobulin within 2 weeks or thrombopoietin receptor agonists within 4 weeks before randomisation were not permitted. Patients were randomly assigned to receive oral daily eltrombopag 50 mg from 21 days preoperatively to postoperative day 7 or intravenous immunoglobulin 1 g/kg or 2 g/kg 7 days before surgery. Eltrombopag dose adjustments were allowed weekly based on platelet counts. The randomisation sequence was generated by a computerised random number generator, concealed and stratified by centre and surgery type (major or minor). The central study statistician was masked to treatment allocation. The primary outcome was achievement of perioperative platelet count targets (90 × 10(9) cells per L before major surgery or 45 × 10(9) cells per L before minor surgery) without rescue treatment. We did intention-to-treat and per-protocol analyses using an absolute non-inferiority margin of -10%. This trial is registered with ClinicalTrials.gov, NCT01621204. FINDINGS Between June 5, 2013, and March 7, 2019, 92 patients with immune thrombocytopenia were screened, of whom 74 (80%) were randomly assigned: 38 to eltrombopag and 36 to intravenous immunoglobulin. Median follow-up was 50 days (IQR 49-55). By intention-to-treat analysis, perioperative platelet targets were achieved for 30 (79%) of 38 patients assigned to eltrombopag and 22 (61%) of 36 patients assigned to intravenous immunoglobulin (absolute risk difference 17·8%, one-sided lower limit of the 95% CI 0·4%; p(non-inferiority)=0·005). In the per-protocol analysis, perioperative platelet targets were achieved for 29 (78%) of 37 patients in the eltrombopag group and 20 (63%) of 32 in the intravenous immunoglobulin group (absolute risk difference 15·9%, one-sided lower limit of the 95% CI -2·1%; p(non-inferiority)=0·009). Two serious adverse events occurred in the eltrombopag group: one treatment-related pulmonary embolism and one vertigo. Five serious adverse events occurred in the intravenous immunoglobulin group (atrial fibrillation, pancreatitis, vulvar pain, chest tube malfunction and conversion to open splenectomy); all were related to complications of surgery. No treatment-related deaths occurred. INTERPRETATION Eltrombopag is an effective alternative to intravenous immunoglobulin for perioperative treatment of immune thrombocytopenia. However, treatment with eltrombopag might increase risk of thrombosis. The decision to choose one treatment over the other will depend on patient preference, resource limitations, cost, and individual risk profiles. FUNDING GlaxoSmithKline and Novartis.
2.
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.
3.
A randomized trial on the efficacy of an autologous blood drainage and transfusion device in patients undergoing elective knee arthroplasty
Heddle NM, Brox WT, Klama LN, Dickson LL, Levine MN
Transfusion. 1992;32((8):):742-6.
Abstract
The purpose of the study reported here was the determination of the efficacy of a postoperative autologous blood drainage and transfusion device in reducing allogeneic red cell requirements in patients undergoing elective knee arthroplasty. The study was a randomized controlled trial with adult patients undergoing unilateral elective arthroplastic knee surgery. Patients underwent suction drainage, attached to an autologous blood drainage and transfusion device, or standard suction drainage. Allogeneic red cells were given according to strict transfusion guidelines based on blood loss and postoperative hemoglobin values. Outcome measures included the mean number of allogeneic red cell concentrates required and the number of patients in each group who required no transfusion. Patients assigned to standard suction drainage had a mean allogeneic red cell utilization of 1.2 units (SD 1.0), as compared to a mean of 0.4 units (SD 0.8) in the group undergoing drainage with the autologous blood drainage and transfusion device (p = 0.0007). The percentage of patients not requiring allogeneic red cells was significantly higher in the latter group (74.3% vs. 32.5%; p = 0.002). The postoperative drainage and transfusion device was efficacious in reducing the amount of allogeneic red cells required by patients undergoing knee arthroplasty, and its use resulted in a 42 percent reduction in the number of patients requiring allogeneic transfusion.