Therapy of Adults Affected By Idiopathic Thrombocytopenic Purpura with 3 Cycles Pulses of High-Dose Dexamethasone (HD-DXM): A Prospective Randomized Clinical Trial

Introduction : Idiopathic thrombocytopenic purpura(ITP) is an autoimmune disorder characterized by platelet destruction leading to decreased platelet count and an increased risk of bleeding. The first line treatment of ITP is still corticosteroid therapy. Prednisone (PDN) is the standard corticosteroid therapy in ITP practical guideline. Recent studies suggested pulsed high-dose dexamethasone (HD-DXM) given at a dose 40 mg/day to a 4-day course treatment as an alternative corticosteroid to reduce the duration and the adverse effect of corticosteroid therapy. In this randomized controlled clinical trial our aim was to compare the efficacy and the relapse free survival time of 3 therapy cycles of HD-DXM versus conventional treatment with PDN for untreated adult patients with ITP.

Method : This was a monocenter, randomized, controlled , clinical trial approved by ethics committee on medical research in Isfahan University of Medical Sciences(IUMS) and also registered in clinical trial.gov( NCT02914054). The eligible patients for this study were aged 18 or older of both genders with newly diagnosed primary ITP according to the international working group (IWG) guideline .Eligible patients were randomly assigned to either enroll conventional Prednisone therapy or pulses of high dose Dexamethasone (HD-DXM) treatment. In HD-DXM arm, DXM was administered intravenously at 40 mg in 500cc normal saline (0.9% saline) during 1 hour for consecutive 4 days and then stopped. This cycle was repeated in 14 days interval to receive 3 cycles of treatment. Patients in PDN arm received PDN orally at 1.0 mg/kg body weight daily for 4 consecutive weeks. After achieving responses the medication tapered gradually to less than 15mg daily or terminated over 4-6 weeks aimed at maintaining platelet count over 30 ×10⁹/L. Cell blood count was performed every week in the first month of treatment and then each month to 1 one year or until loss of response. Baseline parameters such as platelet count were compared between two arms by Fisher exact test. A logistic regression model was used to evaluate the correlation between response and baseline parameters. All patients entered to study provided written informed consent in accordance with the Declaration of Helsinki.

Results : 36 cases were given high dose Dexamethasone another 36 cases were given prednisone as control group. The following results were obtained: (1) at the end of the 3rd cycle, the overall response rate was higher in the HD-DXM group than in the prednisone group; (2) the relapse rate of the HD-DXM group was lower than the control group after 12 months discontinuation;(3) Adverse effect of corticosteroid therapy was less than the control group (p value<0.05).

Conclusion : Treatment with 3 cycles of HD-DXM pulses is an effective method for untreated ITP patients with less adverse effect of corticosteroid in comparison with conventional prednisone therapy.