COHELLP: collaborative randomized controlled trial on corticosteroids in HELLP syndrome

Leila Katz, Melania Amorim, João P Souza, Samira M Haddad, José G Cecatti, COHELLP Study Group, Luciana Pinheiro, Ivelyne R Araújo, Vera T Borges, Shirley K Bruno, Marcia P Bueno, Ricardo C Cavalli, Maria L Costa, Isabela Coutinho, Tábata Z Dias, Francisco E Feitosa, André V Florentino, Gilberto Gomes, Débora F Leite, Claudiney C Lotufo, Fátima A Lotufo, Nelson L Maia Filho, Coríntio Mariani Mariani, Sérgio Martins-Costa, Elias F Melo Jr, Maria R Mesquita, Olímpio Moraes, Joaquim L Moreira, Daniela Nacarato, Bianca Nóbrega, Mary A Parpinelli, José C Peraçoli, Lúcia C Pfitscher, João L Pinto e Silva, Silvana M Quintana, José G Ramos, Marcos A Santos, Nelson Sass, Luiza E Schmaltz, Ricardo P Tedesco, Douglas B Tiago, Leila Katz, Melania Amorim, João P Souza, Samira M Haddad, José G Cecatti, COHELLP Study Group, Luciana Pinheiro, Ivelyne R Araújo, Vera T Borges, Shirley K Bruno, Marcia P Bueno, Ricardo C Cavalli, Maria L Costa, Isabela Coutinho, Tábata Z Dias, Francisco E Feitosa, André V Florentino, Gilberto Gomes, Débora F Leite, Claudiney C Lotufo, Fátima A Lotufo, Nelson L Maia Filho, Coríntio Mariani Mariani, Sérgio Martins-Costa, Elias F Melo Jr, Maria R Mesquita, Olímpio Moraes, Joaquim L Moreira, Daniela Nacarato, Bianca Nóbrega, Mary A Parpinelli, José C Peraçoli, Lúcia C Pfitscher, João L Pinto e Silva, Silvana M Quintana, José G Ramos, Marcos A Santos, Nelson Sass, Luiza E Schmaltz, Ricardo P Tedesco, Douglas B Tiago

Abstract

Background: Hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome is one of the most severe forms of preeclampsia and aggravates both maternal and perinatal prognosis. The systematic review available in Cochrane Library compared corticosteroid (dexamethasone, betamethasone, or prednisolone) given during pregnancy, just after delivery or in the postnatal period, or both before and after birth, with placebo or no treatment. Those receiving steroids showed significantly greater improvement in platelet counts which was greater for those receiving dexamethasone than those receiving betamethasone. There was no clear evidence of any effect of corticosteroids on substantive clinical outcomes. These benefits appear to be greater in Class I HELLP syndrome.

Objectives: To determine the effectiveness of dexamethasone for accelerating postpartum recovery in patients with Class I HELLP syndrome in a multicenter randomized controlled trial.

Methods/design: The study is a triple blind randomized controlled trial including women with class I HELLP syndrome, and exclusion criteria were dexamethasone use in the last 15 days before diagnosis of HELLP syndrome; chronic use of corticosteroids; chronic diseases that alter laboratory parameters of HELLP Syndrome, such as chronic liver disease or purpura, patients unable to consent (coma or critical clinical condition) and without accompanying persons that may consent to study participation.Eligible patients will be invited to participate and those who agree will be included in the study and receive placebo or dexamethasone according to a random list of numbers and subjects will receive the study medication every 12 hours for two days.During the study the women will be subject to strict control of blood pressure and urine output. Laboratory tests will be performed at regular intervals during treatment and 24 hours and 48 hours after its suspension. If worsening of clinical or laboratory variables is observed, a rescue scheme of dexamethasone will be administrated. This proposal has already obtained approval of the local Institutional Review Board of the coordinating center (IMIP, Recife, Brazil), all other participating centers and of the National Council for Ethics in Research (CONEP) of the Brazilian Ministry of Health.

Trial registration: Clinical Trials Register under the number NCT00711841.

Figures

Figure 1
Figure 1
Study design and population (CONSORT, 2010)[19].

References

    1. Sibai BM. The HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): much ado about nothing? Am J Obstet Gynecol. 1990;162:311–316. doi: 10.1016/0002-9378(90)90376-I.
    1. Magann EF, Bass D, Chauhan SP, Sullivan DL, Martin RW, Martin JN Jr. Antepartum corticosteroids: disease stabilization in patients with the syndrome of hemolysis, elevated liver enzymes and low platelets (HELLP) Am J Obstet Gynecol. 1994;171:1148–1153. doi: 10.1016/0002-9378(94)90054-X.
    1. Vigil-De Gracia PE, Tenorio-Maroñón RF, Cejudo-Carranza E, Helguera-Martinez A, García-Cáceres E. Differences among preeclampsia, HELLP syndrome and eclampsia. Maternal Evaluation. Ginecol Obstet Mex. 1996;64:337–382.
    1. Maggann EF, Martin JN Jr. Twelve steps to optimal management of HELLP syndrome. Clin Obstet Gynecol. 1999;42:532–550. doi: 10.1097/00003081-199909000-00009.
    1. Thiagarajah S, Bourgeois FJ, Harbert GM Jr, Caudle MR. Thrombocytopenia in preeclampsia: associated abnormalities and management principles. Am J Obstet Gynecol. 1984;150:1–7.
    1. Yalcin OT, Sener T, Hassa H, Ozalp S, Okur A. Effects of postpartum corticosteroids in patients with HELLP syndrome. Int J Gynecol Obstet. 1998;61:141–148. doi: 10.1016/S0020-7292(98)00036-8.
    1. Suresh MS. HELLP syndrome: An anesthesiologist's perspective. Anesth Clin North Am. 1998;16:332–348.
    1. O´Brien JM, Shumate SA, Satchwell SL, Milligan DA, Barton JR. Maternal benefit of corticosteroids therapy in patients with HELLP (hemolysis, elevated liver enzymes and low platelets count) syndrome: Impact on the rate of regional anesthesia. Am J Obstet Gynecol. 2002;186:475–479. doi: 10.1067/mob.2002.121074.
    1. Heyborne KD, Burke MS, Porreco RP. Prolongation of premature gestation in women with hemolysis, elevated liver enzymes and low platelets. A report of five cases. J Reprod Med. 1990;35:53–57.
    1. Magann EF, Washburne JF, Sullivan CA, Chauhan SP, Morrison JC, Martin JN Jr. Corticosteroid-induced arrest of HELLP syndrome progression in a marginally-viable pregnancy. Eur J Obstet Gynecol Reprod Biol. 1995;59:217–219. doi: 10.1016/0028-2243(94)01995-J.
    1. Heller CS, Elliott JP. High-order multiple pregnancies complicated by HELLP syndrome. A report of four cases with corticosteroid therapy to prolong gestation. J Reprod Med. 1997;42:743–746.
    1. Dreyfus M, Tissier I, Ndocko MA, Denoual I, Baldauf JJ, Ritter J. Corticosteroid therapy for conservative management in marginally-viable pregnancy complicated by HELLP syndrome. Eur J Obstet Gynecol Reprod Biol. 1999;85:233–234. doi: 10.1016/S0301-2115(99)00022-6.
    1. Schlembach D, Munz W, Fischer T. Effect of corticosteroids on HELLP syndrome: a case report. J Perinat Med. 2000;28:502–505.
    1. Fonseca JE, Mendez F, Catano C, Arias F. Dexamethasone treatment does not improve the outcome of women with HELLP syndrome: a double-blind, placebo-controlled, randomized clinical trial. Am J Obstet Gynecol. 2005;193:1591–1598. doi: 10.1016/j.ajog.2005.07.037.
    1. Katz L, Amorim MM, Figueiroa JN, Silva JL Pe. Postpartum dexamethasone for women with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome: a double-blind, placebo-controlled, randomized clinical trial. Am J Obstet Gynecol. 2008;198(3):2.83.e1-8.
    1. Woudstra DM, Chandra S, Hofmeyr GJ, Dowswell T. Corticosteroids for HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in pregnancy. Cochrane Database of Systematic Reviews. The Cochrane Library, Volume 12. 2010. Art. No. CD008148.
    1. Report of the National High Blood Pressure Education Program Working Group on high blood pressure in pregnancy. Am J Obstet Gynecol. 2000;183(1):S1–S22. doi: 10.1067/mob.2000.107928.
    1. OpenClinica® Community Edition: Open source for clinical research. Version 3.1-Community. 2004–2011 Akaza Research LLC and collaborators. .
    1. Schulz KF, Altman DG, Moher D. CONSORT Group. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMC Med. 2010;8:18. doi: 10.1186/1741-7015-8-18.
    1. Brazilian Network of Studies on Reproductive and Perinatal Health. .

Source: PubMed

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