Use of Sildenafil Citrate in Management of Mild Pre-eclampsia

NCT03262961 | Unknown Phase 2 DMC

• 1 other identifier: assiutu252
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

• Mild pre-eclampsia represents 75% of cases with pre-eclampsia, possible progression to severe pre-eclampsia makes mild pre-eclampsia a serious problem that requires attention.
• Previous studies have shown that expectant and conservative management of pre-eclampsia in the context of extreme prematurity may improve perinatal outcomes. Indeed, it has been estimated that for each additional day of pregnancy prolongation between 24 and 32 weeks of gestation, there is a nonlinear corresponding gain of 1% in fetal survival.
• Sildenafil citrate has been used for increasing utero-placental perfusion in cases with intrauterine growth restriction, which makes it a promising drug in management of mild pre-eclampsia.

Conditions

Pre-Eclampsia; Mild

Keywords

Mild pre-eclampsia Sildenafil Citrate

Outcome Measures

Primary Outcomes (1)

• Gestational age at time of termination and maternal outcome.

  Gestational age at time of termination and maternal outcome in terms of whether the disease would progress to severe pre-eclampsia or not.

  up to 37 weeks of gestation

Secondary Outcomes (5)

• Neonatal outcome.

  up to 37 weeks of gestation

• Control of maternal blood pressure.

  up to 37 weeks of gestation

• Method of termination of pregnancy.

  up to 37 weeks of gestation

• Identification of the side effects from the use of sildenafil citrate.

  up to 37 weeks of gestation

• Evaluation of the effect of sildenafil citrate on the feto-maternal circulation through the Doppler ultrasound.

  up to 37 weeks of gestation

Study Arms (2)

Intervention Group

ACTIVE COMPARATOR

• The intervention group will be supplied with Sildenafil Citrate (Respatio® 20mg tablets manufactured by Pharma Right Group , Egypt) according to the patient's weight by the rate of (1.5 mg/kg/day) divided into three doses per day ( every 8 hours) till termination of pregnancy.

Drug: Sildenafil 20 MG

Control Group

PLACEBO COMPARATOR

\- The control group will be supplied with a placebo drug that has the same shape, size and color but without the active ingredient and it would also be taken in a similar way. The placebo tablet will be manufactured at the faculty of pharmacy, Assiut University.

Drug: Placebo Oral Tablet

Interventions

Sildenafil 20 MG DRUG

Also known as: Sildenafil Citrate 20 mg ( Respatio® 20 mg)

Intervention Group

Placebo Oral Tablet DRUG

Also known as: Placebo drug

Control Group

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Pregnant females
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Uncomplicated mild pre-eclampsia; No clinical or investigatory findings suggestive severe pre-eclamptic toxemia.
• Gestational age of 28 - 36 weeks by good dates according to ACOG's - committee on obstetric practice - Method for Estimating Due Date (2014) who will receive the study's drug for at least one week before termination.
• Singleton viable pregnancy.
• Age: 18-35 years.

You may not qualify if:

• Severe pre-eclamptic toxemia (according to the NICE guidelines (2010): Hypertension in pregnancy: diagnosis and management)
• Intrauterine growth retardation.
• Use of medication that could interact with sildenafil citrate such as nitrates erythromycin, ketoconazole, itraconazole, antiretroviral agents and others.
• Presence of maternal co-morbidity disease as: DM, chronic hypertension, congestive heart failure, chronic kidney disease and SLE.
• Placenta previa.
• The patient is using aspirin.
• The presence of a contraindication to the use of sildenafil citrate:
• Hypersensitivity to sildenafil citrate or any of the tablet ingredients.
• Patients with severe cardiovascular disease such as established cardiac failure and unstable angina pectoris.
• Previous episode of non-arteritic anterior ischaemic optic neuropathy.
• Severe hepatic impairment.
• Hypotension (blood pressure \<90/50 mmHg).
• Hypertension (blood pressure \>170/110 mmHg).
• Recent history of stroke or myocardial infarction.
• Known hereditary degenerative retinal disorders such as retinitis pigmentosa.

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Assiut Univeristy Hospitals

Asyut, 71111, Egypt

RECRUITING

Related Publications (29)

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  PMID: 22848831 BACKGROUND

• El-Moselhy, E; Khalifa, H; Amer, S (2011). "Risk Factors and Impacts of Pre-Eclampsia: An Epidemiological Study among Pregnant Mothers in Cairo, Egypt" J Am Sci 7(5): 311-323.

  BACKGROUND

• Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet. 2010 Aug 21;376(9741):631-44. doi: 10.1016/S0140-6736(10)60279-6. Epub 2010 Jul 2.

  PMID: 20598363 BACKGROUND

• Khan KS, Wojdyla D, Say L, Gulmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet. 2006 Apr 1;367(9516):1066-1074. doi: 10.1016/S0140-6736(06)68397-9.

  PMID: 16581405 BACKGROUND

• Campbell OM, Graham WJ; Lancet Maternal Survival Series steering group. Strategies for reducing maternal mortality: getting on with what works. Lancet. 2006 Oct 7;368(9543):1284-99. doi: 10.1016/S0140-6736(06)69381-1.

  PMID: 17027735 BACKGROUND

• Roberts JM, Cooper DW. Pathogenesis and genetics of pre-eclampsia. Lancet. 2001 Jan 6;357(9249):53-6. doi: 10.1016/s0140-6736(00)03577-7.

  PMID: 11197372 BACKGROUND

• Arulkumaran N, Lightstone L. Severe pre-eclampsia and hypertensive crises. Best Pract Res Clin Obstet Gynaecol. 2013 Dec;27(6):877-84. doi: 10.1016/j.bpobgyn.2013.07.003. Epub 2013 Aug 17.

  PMID: 23962474 BACKGROUND

• Mustafa R, Ahmed S, Gupta A, Venuto RC. A comprehensive review of hypertension in pregnancy. J Pregnancy. 2012;2012:105918. doi: 10.1155/2012/105918. Epub 2012 May 23.

  PMID: 22685661 BACKGROUND

• Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000 Jul;183(1):S1-S22.

  PMID: 10920346 BACKGROUND

• Sibai BM. Magnesium sulfate prophylaxis in preeclampsia: Lessons learned from recent trials. Am J Obstet Gynecol. 2004 Jun;190(6):1520-6. doi: 10.1016/j.ajog.2003.12.057.

  PMID: 15284724 BACKGROUND

• Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists' Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5):1122-1131. doi: 10.1097/01.AOG.0000437382.03963.88. No abstract available.

  PMID: 24150027 BACKGROUND

• Sibai BM, Mercer BM, Schiff E, Friedman SA. Aggressive versus expectant management of severe preeclampsia at 28 to 32 weeks' gestation: a randomized controlled trial. Am J Obstet Gynecol. 1994 Sep;171(3):818-22. doi: 10.1016/0002-9378(94)90104-x.

  PMID: 8092235 BACKGROUND

• Haddad B, Deis S, Goffinet F, Paniel BJ, Cabrol D, Siba BM. Maternal and perinatal outcomes during expectant management of 239 severe preeclamptic women between 24 and 33 weeks' gestation. Am J Obstet Gynecol. 2004 Jun;190(6):1590-5; discussion 1595-7. doi: 10.1016/j.ajog.2004.03.050.

  PMID: 15284743 BACKGROUND

• Manktelow BN, Seaton SE, Field DJ, Draper ES. Population-based estimates of in-unit survival for very preterm infants. Pediatrics. 2013 Feb;131(2):e425-32. doi: 10.1542/peds.2012-2189. Epub 2013 Jan 14.

  PMID: 23319523 BACKGROUND

• Cauli O, Herraiz S, Pellicer B, Pellicer A, Felipo V. Treatment with sildenafil prevents impairment of learning in rats born to pre-eclamptic mothers. Neuroscience. 2010 Dec 1;171(2):506-12. doi: 10.1016/j.neuroscience.2010.08.065. Epub 2010 Sep 9.

  PMID: 20832451 BACKGROUND

• Coppage KH, Sun X, Baker RS, Clark KE. Expression of phosphodiesterase 5 in maternal and fetal sheep. Am J Obstet Gynecol. 2005 Sep;193(3 Pt 2):1005-10. doi: 10.1016/j.ajog.2005.05.054.

  PMID: 16157102 BACKGROUND

• Samangaya RA, Mires G, Shennan A, Skillern L, Howe D, McLeod A, Baker PN. A randomised, double-blinded, placebo-controlled study of the phosphodiesterase type 5 inhibitor sildenafil for the treatment of preeclampsia. Hypertens Pregnancy. 2009 Aug;28(4):369-82. doi: 10.3109/10641950802601278.

  PMID: 19843000 BACKGROUND

• Trapani A Jr, Goncalves LF, Trapani TF, Franco MJ, Galluzzo RN, Pires MM. Comparison between transdermal nitroglycerin and sildenafil citrate in intrauterine growth restriction: effects on uterine, umbilical and fetal middle cerebral artery pulsatility indices. Ultrasound Obstet Gynecol. 2016 Jul;48(1):61-5. doi: 10.1002/uog.15673.

  PMID: 26279411 BACKGROUND

• Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, Fleming T, Parpia T, Burgess G, Branzi A, Grimminger F, Kurzyna M, Simonneau G; Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005 Nov 17;353(20):2148-57. doi: 10.1056/NEJMoa050010.

  PMID: 16291984 BACKGROUND

• ACOG Practice bulletin no. 134: fetal growth restriction. Obstet Gynecol. 2013 May;121(5):1122-1133. doi: 10.1097/01.AOG.0000429658.85846.f9.

  PMID: 23635765 BACKGROUND

• Matt H, Nigel J. (2016) "Renal disease in pregnancy" ;Obstet Gynaecol Reprod Med; 26:46-52

  BACKGROUND

• Dastjerdi MV, Hosseini S, Bayani L. Sildenafil citrate and uteroplacental perfusion in fetal growth restriction. J Res Med Sci. 2012 Jul;17(7):632-6.

  PMID: 23798922 RESULT

• McKeeman GC, Ardill JE, Caldwell CM, Hunter AJ, McClure N. Soluble vascular endothelial growth factor receptor-1 (sFlt-1) is increased throughout gestation in patients who have preeclampsia develop. Am J Obstet Gynecol. 2004 Oct;191(4):1240-6. doi: 10.1016/j.ajog.2004.03.004.

  PMID: 15507947 RESULT

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  PMID: 8623789 RESULT

• Lees C, Valensise H, Black R, Harrington K, Byiers S, Romanini C, Campbell S. The efficacy and fetal-maternal cardiovascular effects of transdermal glyceryl trinitrate in the prophylaxis of pre-eclampsia and its complications: a randomized double-blind placebo-controlled trial. Ultrasound Obstet Gynecol. 1998 Nov;12(5):334-8. doi: 10.1046/j.1469-0705.1998.12050334.x.

  PMID: 9819872 RESULT

• Trapani A Jr, Goncalves LF, Pires MM. Transdermal nitroglycerin in patients with severe pre-eclampsia with placental insufficiency: effect on uterine, umbilical and fetal middle cerebral artery resistance indices. Ultrasound Obstet Gynecol. 2011 Oct;38(4):389-94. doi: 10.1002/uog.8983.

  PMID: 21374750 RESULT

• Wareing M, Myers JE, O'Hara M, Baker PN. Sildenafil citrate (Viagra) enhances vasodilatation in fetal growth restriction. J Clin Endocrinol Metab. 2005 May;90(5):2550-5. doi: 10.1210/jc.2004-1831. Epub 2005 Feb 15.

  PMID: 15713717 RESULT

• Trapani A Jr, Goncalves LF, Trapani TF, Vieira S, Pires M, Pires MMS. Perinatal and Hemodynamic Evaluation of Sildenafil Citrate for Preeclampsia Treatment: A Randomized Controlled Trial. Obstet Gynecol. 2016 Aug;128(2):253-259. doi: 10.1097/AOG.0000000000001518.

  PMID: 27400005 RESULT

MeSH Terms

Conditions

Pre-Eclampsia; Lymphoma, Follicular

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Fady Abdallah

  Assiut University

  PRINCIPAL INVESTIGATOR

• Hasan Kamel

  Assiut University

  STUDY DIRECTOR

• Hisham Abou-Taleb

  Assiut University

  STUDY DIRECTOR

Central Study Contacts

Fady Abdallah

CONTACT

00201002837042; fady.nasif@yahoo.com

Hisham Abou-Taleb

CONTACT

00201003332139; hishamaboutaleb1@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: \- It's a double blinded, randomized, placebo-controlled trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident of Obstetrics and Gynecology Department - Assiut University

Model Details: \- Double blinded, randomized, placebo-controlled trial.

Study Record Dates

• First Submitted: August 19, 2017
• First Posted: August 28, 2017
• Study Start: September 15, 2016
• Primary Completion: December 15, 2017
• Study Completion: January 15, 2018
• Last Updated: August 28, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)