Clonidine versus captopril for treatment of postpartum very high blood pressure: study protocol for a randomized controlled trial (CLONCAP)

Reproductive Health

Melania Maria Ramos Amorim¹  Alex Sandro Rolland Souza²  Sabina B Maia²  Isabela C Coutinho²  Leila Katz²  Carlos Noronha-Neto² 

[1] Department of Obstetrics and Gynecology, Federal University of Campina Grande, Campina Grande, PB, Brazil;Obstetric Intensive Care Unit, Instituto de Medicina Integral Prof. Fernando Figueira, Recife, PE, Brazil

关键词: Antihypertensive agents;    Randomized controlled trial;    Very high blood pressure;    Postpartum;    Pregnancy;    Hypertension;    Severe preeclampsia;   

Others  :  811442
DOI  :  10.1186/1742-4755-10-37

 received in 2013-07-07, accepted in 2013-07-29,  发布年份 2013

【 摘 要 】

Background

The behavior of arterial blood pressure in postpartum of women with hypertension and pregnancy and the best treatment for very high blood pressure in this period still need evidence. The Cochrane systematic review assessing prevention and treatment of postpartum hypertension found only two trials (120 patients) comparing hydralazine with nifedipine and labetalol for the treatment of severe hypertension and did not find enough evidence to know how best to treat women with hypertension after birth. Although studies have demonstrated the effectiveness of treatment with captopril, side effects were reported. Because of these findings, new classes of antihypertensive drugs began to be administered as an alternative therapy. Data on the role of clonidine in this particular group of patients, its effects in the short and long term are still scarce in the literature.

Objectives

To determine the effectiveness of clonidine, compared to captopril, for the treatment of postpartum very high blood pressure in women with hypertension in pregnancy.

Methods/design

The study is a triple blind randomized controlled trial including postpartum women with diagnosis of hypertension in pregnancy presenting very high blood pressure, and exclusion criteria will be presence of heart disease, smoking, use of illicit drugs, any contraindication to the use of captopril or clonidine and inability to receive oral medications.

Eligible patients will be invited to participate and those who agree will be included in the study and receive captopril or clonidine according to a random list of numbers. The subjects will receive the study medication every 20 minutes until blood pressure is over 170 mmHg of systolic blood pressure and 110 mmHg diastolic blood pressure. A maximum of six pills a day for very high blood pressure will be administered. In case of persistent high blood pressure levels, other antihypertensive agents will be used.

During the study the women will be subject to strict control of blood pressure and urine output. This proposal has already obtained approval of the local Institutional Review Board of the coordinating center (IMIP, Recife, Brazil) and of the National Council for Ethics in Research (CONEP) of the Brazilian Ministry of Health.

Trial registration

Clinical Trials Register under the number NCT01761916.

【 授权许可】

   
2013 Noronha-Neto et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Roberts CL, Ford JB, Algert CS, Antonsen S, Chalmers J, et al.: Population-based trends in pregnancy hypertension and pre-eclampsia: an international comparative study. BMJ Open 2011, 1(1):e000101.
• [2]Goldenberg RL, McClue EM, MacGuire ER, Kamath BD, Jobe AH: Lessons for low-income regions following the reduction in hypertension related maternal mortality in high-income countries. Int J Gynecol Obstet 2011, 113:91-95.
• [3]ACGO: Diagnosis and management of preeclampsia and eclampsia. ACGO Practice Bulletin 2002, 33:1-14.
• [4]Duley L: The global impact of pre-eclâmpsia and eclâmpsia. Semin Perinatol 2009, 33:130-137.
• [5]Barreto S: Factores de riesgo y resultados perinatales en la preeclampsia severa: um estudio caso control. Rev Hosp Matern Infant Ramon Sarda. 2003, 22:116-120.
• [6]Baha M, Sibai MD: Etiology and management of postpartum hypertension-preeclampsia. Am J Obstet Gynecol 2012, 206:470-475.
• [7]Tan L, de Swiet M: The management of postpartum hypertension. BJOG 2002, 109:733-736.
• [8]Chames MC, Livingston JC, Ivester TS, Barton JR, Sibai BM: Late postpartum eclampsia: a preventable disease? Am J Obstet Gynecol 2002, 186:1174-1177.
• [9]Magee L, von Dadelszen P: Prevention and treatment of postpartum hypertension. Cochrane Database Syst Rev 5:CD004351. The Cochrane Library
• [10]Ghuman N, Rhiener J, Tendler BE, White WB: Hypertension in the postpartum woman: clinical update for the hypertension specialist. J Clin Hypertens (Greenwich) 2009, 11:726-733.
• [11]Clark SL, Belfort MA, Dildy GA, Englebright J, Meints L, et al.: Emergency department use during the postpartum period: implications for current management of the puerperium. Am J Obstet Gynecol 2010, 203(38):e1-e6.
• [12]Wallis AB, Saftlas AF, Hsia J, Atrash HK: Secular trends in the rates of preeclampsia, eclampsia, and gestational hypertension, United States, 1987–2004. Am J Hypertens 2008, 21:521-526.
• [13]Douglas KA, Redman CWG: Eclampsia in the United Kingdom. BMJ 1994, 309:1395-1400.
• [14]Sanctos M: Evolução dos níveis pressóricos no puerpério em mulheres com pré-eclâmpsia grave atendidas em um hospital terciário: estudo de coorte [dissertação]. Recife: Instituto de Medicina Integral Professor Fernando Figueira-IMIP; 2004.
• [15]Davison JM, Dunlop W: Changes in renal hemodynamics and tubular function induced by human normal pregnancy. Semin Nephrol 1984, 4:198-207.
• [16]Bond AL, August P, Druzin M, Atlas SA, Sealey JE, et al.: Atrial natriuretic factor in normal and hypertensive pregnancy. Am J Obstet Gynecol 1989, 160:1112-1116.
• [17]Castro LC, Hobel CJ, Gornbein J: Plasma levels of atrial natriuretic peptide in normal and hypertensive pregnancies: a meta-analysis. Am J Obstet Gynecol 1994, 171:1642-1651.
• [18]National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy: 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.
• [19]Firoz T, Melnik T: Postpartum evaluation and long term implications. Best Pract Res Clin Obstet Gynaecol 2011, 25(4):549-561.
• [20]Lambot MA, Vermeylen D, Noel JC: Angiotensin-II receptor inhibitors in pregnancy. Lancet 2001, 357:1619-1620.
• [21]Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, et al.: Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med 2006, 354:2443-2451.
• [22]Vásquez D, Quijano F, Durán M: Uso del captopril en la crisis hipertensiva inducida por el embarazo. Rev Colomb Obstet Ginecol 1995, 46(1):41-47.
• [23]Devlin RG, Fleiss PM: Captopril in human blood and breast milk. J Clin Pharmacol 1981, 21:110-113.
• [24]Germany PL, Martins SC: Tratamento anti-hipertensivo na gestação e lactação. Femina 2003, 31(9):803-808.
• [25]Drummer OH, Jarrott B: The disposition and metabolism of captopril. Med Res Rev 1986, 6:86-90.
• [26]Zuspan FP: Problems encountered in the treatment of pregnancy-induced-hypertension. A point of view. Am J Obstet Gynecol 1978, 131:591-597.
• [27]Podymow T, August P: Antihypertensive drugs in pregnancy. Semin Nephrol 2011, 31:70-85.
• [28]Hartikainen-Sorri AL, Heikkinen JE, Koivisto M: Pharmacokinetics of clonidine during pregnancy and nursing. Obstet Gynecol 1987, 69:598-600.
• [29]Bunjes R, Schaefer C, Holzinger D: Clonidine and breast-feeding. Clin Pharm 1993, 12:178-179.
• [30]Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, Hróbjartsson A, Mann H, Dickersin K, Berlin J, Doré C, Parulekar W, Summerskill W, Groves T, Schulz K, Sox H, Rockhold FW, Rennie D, Moher D: SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med 2013, 158:200-207.
• [31]Schulz KF, Altman DG, Moher D: CONSORT Group: CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMC Med 2010, 8:18. BioMed Central Full Text