Comparative Study of Intravenous Labetalol Versus Intravenous Nitroglycerin Versus Sublingual Nifedipine

A Comparative Study of Intravenous Labetalol Versus Intravenous Nitroglycerin Versus Sublingual Nifedipine to Control Blood Pressure in Severe Pre-eclampsia

Pre-eclampsia (PE) is one of the most frequent pregnancy complications and is one of the main causes of maternal and fetal morbidity and mortality in its severe form.control of blood pressure is of crucial importance to avoid maternal and fetal complications.Therapeutic modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction could help to ameliorate the systemic manifestations in patients with severe PE. Either Intravenous labetalol and nitroglycerine as well as sublingual nifedipine have been frequantly used for the management of acute severe hypertension in PE

Study Overview

• Status: Not yet recruiting
• Conditions: Severe Preeclampsia
• Intervention / Treatment: Drug: Labetalol; Drug: Nitroglycerine; Drug: Nifedipine

Detailed Description

Pre-eclampsia (PE) is one of the most frequent pregnancy complications and is one of the main causes of maternal and fetal morbidity and mortality in its severe form.

Pre-eclampsia characterized by

• Rising blood pressure (BP ≥ 140/90 that occurs after 20 weeks of gestation in a woman with previously normal BP.
• . Proteinuria (≥300mg/24hr . This correlates with 30mg/dl or ≥1+ on urine dipstick)
• Edema control of blood pressure is of crucial importance to avoid maternal and fetal complications.

The pathophysiology of pre-eclampsia is most likely inadequate placentation, leading to endothelial dysfunction and reduced nitric oxide bioavailability. Therapeutic modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction could help to ameliorate the systemic manifestations in patients with severe PE. Either Intravenous labetalol and nitroglycerine as well as sublingual nifedipine have been frequantly used for the management of acute severe hypertension in PE

. Nitroglycerine, a nitric oxide donor with low oral bioavailability and a very short half-life, has a potent venodilator effect in low doses and affects arterial tone at high doses Labetalol is useful as it contains both selective, competitive, alpha1-adrenergic antagonism and non-selective, competitive, beta-adrenergic (B1 and B2) blocking activity in a single agent Nifedipine is a dihydropyridine calcium channel blocker. Its main uses are as an antianginal and antihypertensive

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: fawzy A badawy, assistant professor; Phone Number: 01004862474
• Study Contact Backup: Name: diaa A abdelaal, resident; Phone Number: 01064451169; Email: deaaaly@med.sohag.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The study will include 60 adult female patients ( 18 to 40 years old) with sever pre-eclampsia, who were being managed with MgSO4 loading and maintenance doses Severe hypertension was diagnosed by Systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥110 mmHg.

Mean arterial blood pressure ≥ 127 mmHg

Exclusion Criteria:

1. Patient refusal.
2. Eclampsia
3. Emenant eclampsia
4. HELLP syndrome
5. Chronic hypertension
6. Patients who have chronic obstructive pulmonary disease.
7. Patient with acute or chronic liver failure.
8. Known allergy to the study medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: group A; (20 patients) will receive Labetalol intravenous infusion. The starting infusion rate is 5mg/h,the infusion rate will be changed 1mg/h up every 10 minutes until the desired goal achieved which is a decrease in systolic blood pressure (SBP) to 120 - 140 mmHg and a decrease in diastolic blood pressure (DBP) to 80 - 90 mmHg every 10 minutes	Drug: Labetalol; it contains both selective, competitive, alpha1-adrenergic antagonism and non-selective, competitive, beta-adrenergic (B1 and B2) blocking activity in a single agent
Active Comparator: group B; (20 patients) will receive calculated dose of Nitroglycerine started as intravenous infusion, The starting infusion rate is 4.8mg/h ,the infusion rate will be changed 1mg/h every 10 minutes up until the therapeutic goal achieved, which is a decrease in systolic blood pressure (SBP) to 120 - 140 mmHg and a decrease in diastolic blood pressure (DBP) to 80 - 90 mmHg	Drug: Nitroglycerine; a nitric oxide donor with low oral bioavailability and a very short half-life, has a potent venodilator effect in low doses and affects arterial tone at high doses
Active Comparator: group C; , (20 patients) will receive calculated dose of nifedipine the content (100 µL) of a 10 mg capsule of nifedipine was drawn up into an insulin syringe and deposited sublingually, every 30 min.( Maximum dose of nifedipine 120 mg/day) ) until the therapeutic goal achieved, which is a decrease in systolic blood pressure (SBP) to 120 - 140 mmHg and a decrease in diastolic blood pressure (DBP) to 80 - 90 mmHg	Drug: Nifedipine; dihydropyridine calcium channel blocker. Its main uses are as an antianginal and antihypertensive

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
duration of control blood pressure	duration required, of nitroglycerin compared to labetalol and sublingual nifedipine in terms of acute control of blood pressure in severe PE.	1 year

Collaborators and Investigators

• Sponsor: Sohag University

Publications and helpful links

General Publications

• Divakaran S, Loscalzo J. The Role of Nitroglycerin and Other Nitrogen Oxides in Cardiovascular Therapeutics. J Am Coll Cardiol. 2017 Nov 7;70(19):2393-2410. doi: 10.1016/j.jacc.2017.09.1064.
• Johal T, Lees CC, Everett TR, Wilkinson IB. The nitric oxide pathway and possible therapeutic options in pre-eclampsia. Br J Clin Pharmacol. 2014 Aug;78(2):244-57. doi: 10.1111/bcp.12301.
• Al-Mulhim AA, Abu-Heija A, Al-Jamma F, El-Harith el-HA. Pre-eclampsia: maternal risk factors and perinatal outcome. Fetal Diagn Ther. 2003 Jul-Aug;18(4):275-80. doi: 10.1159/000070809.
• Olayinka L, Garnett E, Burnett B, Devaraj S. Comparison of random urine protein/creatinine ratio with 24-hour urine protein in suspected pre-eclampsia. Pract Lab Med. 2023 Jun 21;36:e00316. doi: 10.1016/j.plabm.2023.e00316. eCollection 2023 Aug.

Study record dates

Study Major Dates

• Study Start (Estimated): March 30, 2024
• Primary Completion (Estimated): March 30, 2025
• Study Completion (Estimated): March 30, 2025

Study Registration Dates

• First Submitted: February 11, 2024
• First Submitted That Met QC Criteria: February 11, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 11, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Pre-Eclampsia; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Sympathomimetics; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Nitroglycerin; Nifedipine; Labetalol
• Other Study ID Numbers: Soh-Med-24-01-07MS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No