Nifedipine Dosing Daily vs Twice a Day for Pre-eclampsia With Severe Features (NOPPI)

Frequency and Dosing of Long Acting Anti-Hypertensive Agent in Women With Pre-eclampsia With Severe Features Undergoing Expectant Management: A Randomized Controlled Trial

The investigators propose a randomized controlled unblinded trial to evaluate rates of optimal blood pressure control between Nifedipine 60mg XL once daily vs. Nifedipine 30mg XL twice daily in patients admitted for expectant management with pre-eclampsia with severe features. Patients will be approached for consent when they are placed on 30mg of Nifedipine daily by their primary provider and will be enrolled in the study when the primary provider has made the decision to increase the patient's daily dose of Nifedipine XL from 30mg to 60mg.

Study Overview

• Status: Completed
• Conditions: Preeclampsia With Severe Features
• Intervention / Treatment: Drug: Nifedipine XL

Detailed Description

This is a randomized controlled unblinded trial at The Ohio State University comparing Nifedipine XL 60mg daily to 30mg twice daily in patients admitted for expectant management for pre-eclampsia with severe features.

Potential study participants will be identified at the time of admission to the antepartum unit. Inclusion criteria must be met, namely patient's age, gestational age, diagnosis of preeclampsia with severe features.

Patients will be approached for consent when they are placed on 30mg of Nifedipine daily by their primary provider and will be enrolled in the study when the primary provider has made the decision to increase the patient's daily dose of Nifedipine XL from 30mg to 60mg. Participants will be randomized in to one of two groups:

• Once daily Nifedipine XL 60mg Vs.
• Twice daily Nifedipine XL 30mg

Once enrolled and randomized, blood pressures will be monitored every 4 hours as is standard on the antepartum unit. Blood pressures for the primary outcome will be collected 24 hours after the patient is randomized and initiated on their above regimen. This is to allow the medication to reach steady state prior to collected information on optimal blood pressures. The primary outcome will consist of blood pressure values collected q4 hours beginning 24h-48h after receiving their first dose of the randomized dose regimen.

Algorithms for the administration of intravenous labetalol, Nifedipine or hydralazine will be utilized by the primary provider at his or her discretion.

Women may take the medication concurrently with intravenous labetalol, hydralazine, or immediate release Nifedipine for the treatment of severe blood pressures as determined by their primary provider.

All other obstetric care will be at the discretion of the primary provider, including but not limited to addition of second long-acting hypertensive agents, decision to proceed with delivery, IV magnesium for seizure prophylaxis and recommendations regarding mode of delivery. Data will be collected on these components of routine obstetric care. Analysis will be by intent to treat.

A subset of patients will be enrolled for a pharmacokinetic study and blood will be collected at prespecified times following administration of the randomized Nifedipine XL regimen.

• Study Type: Observational
• Enrollment (Actual): 56

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Pregnant women undergoing expectant management for a diagnosis of preeclampsia with severe features already initiated on 30mg Nifedipine XL and the primary provider has made the decision to increase the patient's daily dose of Procardia XL from 30mg to 60mg. .

Description

Inclusion Criteria:

• Women age 18-45 with a viable single or twin intrauterine pregnancy between 22 0/7 and 33 6/7 weeks gestation based on the best obstetric estimate by ACOG criteria.
• Undergoing expectant management for a diagnosis of preeclampsia with severe features and already initiated on 30mg Nifedipine XL. The patient may or may not have already received acute treatment for severe blood pressures.

Exclusion Criteria:

• Known allergy or adverse reaction to Nifedipine or any medical condition where Nifedipine is contraindicated, such as galactose intolerance, severe GI stricture, and GI hypomotility disorder.
• Participation in another trial without prior approval
• Currently receiving a daily dose of Nifedipine XL of 60mg or greater
• Continuation of alternate long-acting anti-hypertensive medication on admission
• Physician/provider or patient refusal
• Triplet or higher order pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Once daily Nifedipine XL 60mg; Participants will receive Nifedipine XL once daily 60 mg for 48 hours.	Drug: Nifedipine XL; Patients will be enrolled when the primary provider has made the decision to increase the patient's daily dose of Procardia XL from 30mg to 60mg. Participants will be randomized in to one of two groups; Once daily Nifedipine XL 60mg Vs.; Twice daily Nifedipine XL 30mg; Other Names: Procardia XL
Twice daily Nifedipine XL 30mg; Participants will receive Nifedipine XL twice daily 30 mg for 48 hours.	Drug: Nifedipine XL; Patients will be enrolled when the primary provider has made the decision to increase the patient's daily dose of Procardia XL from 30mg to 60mg. Participants will be randomized in to one of two groups; Once daily Nifedipine XL 60mg Vs.; Twice daily Nifedipine XL 30mg; Other Names: Procardia XL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparing the rates of suboptimal blood pressure	Comparing the rates of suboptimal blood pressure, defined as frequency of systolic >150 mmHg and/or diastolic >100 mmHg blood pressure. Blood pressure measurements will be measured every 4 hours on day 2 (24 hour-48 hour) after the patient has been enrolled, randomized, and initiated on either once daily Nifedipine XL 60mg or twice daily Nifedipine XL 30mg.	on day 2 (24 hour-48 hour) after the patient has been enrolled

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluating number of route of delivery		Through study completion, an average of 2 years
Evaluating mean systolic and diastolic blood pressure and mean arterial pressure	Evaluating mean systolic and diastolic blood pressure and mean arterial pressure measured on day 2 (24h-48h) after the patient has been enrolled, randomized, and initiated on Nifedipine regimen	on day 2 (24 hour-48 hour) after the patient has been enrolled
Evaluating concentration of Nifedipine in blood	Evaluating concentration of Nifedipine in blood measured at prespecified times taken on day 2 (24 hour-48 hour) after the patient has been enrolled, randomized, and initiated on a Nifedipine regimen	on day 2 (24 hour-48 hour) after the patient has been enrolled
Evaluating number of days in expectant management from enrollment		Through study completion, an average of 2 years
Evaluating frequency of indications for cesarean section		Through study completion, an average of 2 years
Evaluating frequency of need for acute acting anti-hypertensive treatment (IR Nifedipine, IV labetalol, or IV hydralazine)		on day 2 (24 hour-48 hour) after the patient has been enrolled
Evaluating number of delivery less than 34 weeks		Through study completion, an average of 2 years
Evaluating gestational age at delivery		Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Ohio State University
• Investigators: Principal Investigator: Kara Rood, MD, Ohio State University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Actual): December 6, 2023
• Study Completion (Actual): December 15, 2023

Study Registration Dates

• First Submitted: September 17, 2021
• First Submitted That Met QC Criteria: October 26, 2021
• First Posted (Actual): October 27, 2021

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 21, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: preeclampsia severe; Nifedipine XL 60mg; Nifedipine XL 30mg
• Additional Relevant MeSH Terms: Pregnancy Complications; Hypertension, Pregnancy-Induced; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Eclampsia; Pre-Eclampsia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Tocolytic Agents; Nifedipine
• Other Study ID Numbers: 2021H0292

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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