Contents lists available at ScienceDirect Pregnancy Hypertension journal homepage: www.elsevier.com/locate/preghy Dexamethasone for the treatment of class I HELLP syndrome: A double- blind, placebo-controlled, multicenter, randomized clinical trial Javier E. Fonseca a, ⁎ , Juan C Otero b , Clara Messa c a UniversidaddelValle,DepartmentofGynecologyandObstetrics(MUGERresearchgroup)andHospitalUniversitariodelValle,Calle5#36-08.Cali,760042,Colombia b Universidad Industrial de Santander and Hospital Universitario de Santander, Carrera 33 # 28, 126, Bucaramanga 680001, Colombia c Universidad CES and Hospital General de Medellín, Carrera 48 # 32, 102., Medellin 050001, Colombia 1. Introduction HELLP syndrome, characterized by hemolysis, elevated liver en- zymes and low platelet count, is one of the most severe complications of preeclampsia; it is associated with increased frequency of complications such as death, eclampsia and acute renal failure, and a longer hospital stay. Women affected by HELLP syndrome may be classified by the degree of thrombocytopenia into class 1 HELLP syndrome (≤50,000 platelets/mm 3 ); class 2 HELLP syndrome (between 50,000 and 100,000 platelets/mm 3 ); and class 3 HELLP syndrome (between 100,000 and 150,000 platelets/mm 3 ) [1]. Since 1994, several clinical trials have suggested that corticoster- oids, mainly dexamethasone therapy, can ameliorate and stabilize the disease in the antepartum period, and accelerate recovery after delivery [2–5]. Two clinical trials in contrast, one published in 2005 (which included pregnant and postpartum women), and another published in 2008 (which only included postpartum women) [6,7], did not support the use of dexamethasone for the treatment of HELLP syndrome, be- cause their authors did not find differences in duration of hospitaliza- tion, time to recovery of laboratory tests, recovery of clinical para- meters, need for blood transfusion, or frequency of complications. However, we found in an unplanned analysis [6], stratified according to the severity of HELLP syndrome, that the platelet recovery time was heterogeneous when the cases were stratified for HELLP class at the time of enrollment (Mantel –cox test, chi squared 4.76; P = 03) [6]. In this analysis we found that in patients with HELLP 1 who received dexamethasone therapy, the conditional probability of platelet recovery was higher (HR 3.4; 95%CI 1.3–8.5), and the duration of hospitalization was shorter (means 4.6 vs 10.4). Based on these findings, we decided to conduct a study aimed to determine the efficacy of using dex- amethasone, only for the treatment of women affected by HELLP syn- drome class 1. 2. Material and methods This was a double blind, placebo controlled, multicenter randomized clinical trial involving pregnant and postpartum women admitted to three institutions: Hospital Universitario del Valle in Cali, Colombia; Hospital General del Medellin in Medellin, Colombia and Hospital Universitario de Santander in Bucaramanga, Colombia be- tween October 2009 and November 2012. Pregnant women over 20 weeks of gestation or during the first 3 days of puerperium were asked to participate in the study, if they developed hypertension during pregnancy or the puerperium and met the criteria for complete class 1 HELLP syndrome, as defined by Sibai [8]: platelet count ≤50,000/ mm3, aspartate aminotransferase (AST) ≥70 U/L and lactate dehy- drogenase (LDH) ≥ 600 U/L. The recruited patients signed informed consent. Exclusion criteria included: oral temperature > 37.5 °C, dia- betes diagnosis and contraindication to steroids. Because of the po- tential for spontaneous platelet recovery, postpartum women were ex- cluded if randomization was not accomplished during the first 24 h after diagnosis. The study was approved by the Institutional Review Boards of the participating Hospitals and the Medical Schools (Uni- versidad del Valle, approval certificate N 017-08); and it was registered in ClinicalTrial.gov with number NCT 01138839. Pregnant and postpartum women were randomly assigned in a 1:1 ratio to treatment or placebo groups, using a randomized stratification (by center and the status of the patient at the time of admission to the trial, pregnant or postpartum women); randomization was performed in permuted blocks of varying size (4 or 6), and by a person external to this research. The assignment was kept inside consecutively numbered opaque envelopes labeled as pregnant or postpartum, which were opened after obtaining informed consent. Pregnant women in the ex- perimental group received 10-mg doses of dexamethasone sodium phosphate, intravenously, every 12 h until delivery; and 3 additional doses after delivery. Postpartum women received three 10-mg doses after delivery. The same schedule was used for the control group, who were administered sterile water as placebo. Dexamethasone and pla- cebo were packed in identical vials, in sealed boxes that were labeled with the corresponding treatment codes. Codes were not broken until the end of the univariate analysis. Treatment was to be discontinued if oral temperature rose above 37.5 °C https://doi.org/10.1016/j.preghy.2019.06.003 Received 24 March 2019; Received in revised form 10 June 2019; Accepted 16 June 2019 ⁎ Corresponding author. E-mail address: javier.fonseca@correounivalle.edu.co (J.E. Fonseca). Pregnancy Hypertension 17 (2019) 158–164 Available online 17 June 2019 2210-7789/ © 2019 International Society for the Study of Hypertension in Pregnancy. 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