NIFEdipine ER for Reducing High Blood Pressure After Preeclampsia

(REPAIR Trial)

Recruiting at 1 trial location

Overseen By Sadiya Khan, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Disqualifiers: Pre-gestational hypertension, Diabetes, ICU admission, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

618 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well NIFEdipine ER, a blood pressure medication, helps women manage high blood pressure after preeclampsia or other pregnancy-related issues. The researchers aim to determine if better blood pressure control improves long-term heart health and reduces future heart problems. Participants are divided into two groups: one begins the medication at lower blood pressure levels than the other. The trial seeks women who have experienced pregnancy-related high blood pressure issues and are within four days postpartum. As an unphased trial, it offers participants the chance to contribute to valuable research that could enhance postpartum care for women with high blood pressure.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that NIFEdipine ER is likely to be safe for humans?

Research has shown that nifedipine ER is generally safe for use after childbirth, particularly for controlling high blood pressure. Studies have found that nifedipine does not harm babies or affect blood flow to the uterus or umbilical cord, which is crucial for new mothers. Additionally, patients treated with nifedipine for severe preeclampsia experienced fewer episodes of dangerously high blood pressure.

These findings suggest that nifedipine ER is well-tolerated and can effectively manage blood pressure without major side effects, making it a promising option for managing high blood pressure after preeclampsia. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about NIFEdipine ER for postpartum high blood pressure management after preeclampsia because it offers a more intensive approach compared to current options. Unlike the usual care, which starts treatment at a higher blood pressure threshold, NIFEdipine ER is initiated earlier, at a systolic blood pressure of 140 mmHg or a diastolic of 90 mmHg. This proactive strategy aims to maintain lower blood pressure levels, potentially reducing complications and improving recovery during the crucial first six weeks after childbirth.

What evidence suggests that NIFEdipine ER might be an effective treatment for high blood pressure after preeclampsia?

Research shows that Nifedipine ER effectively lowers high blood pressure by relaxing and widening blood vessels, easing the heart's ability to pump blood. Studies indicate that Nifedipine reduces the average arterial pressure by 57.49%, outperforming other common medications like labetalol and hydralazine. In individuals with chronic high blood pressure, Nifedipine has been proven to lower blood vessel pressure over a 24-hour period. This treatment is already approved for managing high blood pressure and stable angina, conditions related to high blood pressure and heart pain. In this trial, participants will join either an experimental arm with intensive postpartum blood pressure control using Nifedipine ER or a control arm with usual care using Nifedipine ER, to evaluate its effectiveness in reducing high blood pressure after preeclampsia. ^{4 6 7 8 9}

Who Is on the Research Team?

Anna Palatnik, MD

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

This trial is for women aged 18-50 who have had high blood pressure or preeclampsia during pregnancy, can communicate in English or Spanish, and are within the first three days after giving birth. It's not for those with pre-pregnancy hypertension or diabetes, planning to transfer hospitals postpartum, allergic to nifedipine, or unable to consent.

Inclusion Criteria

Postpartum day 0-3 and prior to discharge

I was diagnosed with high blood pressure during pregnancy.

Exclusion Criteria

Pre-gestational hypertension

I had diabetes before getting pregnant.

Intent to transfer postpartum to an outside institution of the participating centers

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Intensive postpartum blood pressure control with nifedipine ER initiation for 6 weeks postpartum

6 weeks

Regular visits for blood pressure monitoring

Follow-up

Participants are monitored for cardiovascular health, including BP monitoring and cardiovascular function assessment at 6 weeks and 12 months postpartum

12 months

Visits at 6 weeks and 12 months postpartum

What Are the Treatments Tested in This Trial?

Interventions

• NIFEdipine ER

Trial Overview The study tests whether intensive blood pressure control using NIFEdipine ER after childbirth can improve heart health, lower the risk of long-term high blood pressure, and reverse vascular damage caused by hypertensive disorders during pregnancy.

How Is the Trial Designed?

Group I: REPAIR ARM Experimental Treatment 1 Intervention

Intensive postpartum blood pressure control with nifedipine ER initiation at systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg and maintaining blood pressure \<140/90 mmHg during the first 6 weeks postpartum.

Group II: CONTROL ARM Active Control 1 Intervention

Usual care with nifedipine ER initiation at SBP ≥150 mmHg or DBP ≥100 mmHg and maintaining blood pressure \<150/100 mmHg during the first 6 weeks postpartum.

NIFEdipine ER is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Nifedipine for:

• Hypertension
• Angina pectoris
• Vasospastic angina

Approved in United States as Nifedipine for:

• Hypertension
• Angina pectoris
• Vasospastic angina
• Chronic stable angina

Approved in Canada as Nifedipine for:

• Hypertension
• Angina pectoris
• Vasospastic angina

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

In a study involving 338 women with severe preeclampsia, the combination of nifedipine and phytosterol achieved blood pressure control 13 minutes faster than nifedipine alone and 3 minutes faster than nicardipine, indicating improved efficacy in managing this condition.

The combination treatment of nifedipine and phytosterol resulted in fewer stillbirths and adverse outcomes compared to the nicardipine group, suggesting it may be a safer option for managing severe preeclampsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral nifedipine and phytosterol, intravenous nicardipine, and oral nifedipine only: Three-arm, retrospective, cohort study for management of severe preeclampsia. Ma, S., Zhu, L., Zhou, T., et al.[2023]

In a study of 14 preeclamptic patients experiencing 55 hypertensive emergencies, oral nifedipine was found to reduce blood pressure more quickly than labetalol, taking an average of 31.30 minutes compared to 53.50 minutes (p = 0.03).

Both medications were safe, with no maternal or fetal adverse events reported, indicating that oral nifedipine is not only faster but also at least as safe as labetalol for treating hypertension in preeclampsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trial of oral nifedipine and oral labetalol in preeclampsia hypertensive emergency treatment. Duro-Gómez, J., Rodríguez-Marín, AB., Giménez de Azcárete, M., et al.[2018]

Nifedipine effectively controlled blood pressure in 95.8% of patients with severe preeclampsia, compared to 68% for hydralazine, indicating it is a more effective treatment option.

Patients treated with nifedipine had significantly shorter neonatal intensive care unit stays (15.1 days) compared to those treated with hydralazine (32.7 days), suggesting better outcomes for infants and reduced hospitalization costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nifedipine in the treatment of severe preeclampsia. Fenakel, K., Fenakel, G., Appelman, Z., et al.[2013]

In a randomized trial involving 110 participants with preeclampsia, the use of extended-release nifedipine significantly reduced the need for acute hypertension treatment during labor, with a relative risk of 0.62 compared to placebo.

The nifedipine group also had a lower rate of cesarean deliveries (20.8% vs. 34.7%) and fewer admissions to the neonatal intensive care unit (29.1% vs. 47.1%), suggesting potential benefits for both maternal and neonatal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial of Intrapartum Extended-Release Nifedipine to Prevent Severe Hypertension Among Pregnant Individuals With Preeclampsia With Severe Features. Cleary, EM., Racchi, NW., Patton, KG., et al.[2023]

In a study involving 626 patients with preeclampsia, the combination of celastrol and nifedipine significantly reduced the time needed to control hypertension and increased the duration before another hypertensive crisis compared to nifedipine alone.

The combination treatment also required fewer doses to manage hypertension without increasing adverse effects for mothers or newborns, suggesting celastrol is a safe and effective addition to nifedipine therapy for preeclampsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Celastrol synergizes with oral nifedipine to attenuate hypertension in preeclampsia: a randomized, placebo-controlled, and double blinded trial. Xiao, S., Zhang, M., Liang, Y., et al.[2021]

Nifedipine effectively controlled high blood pressure in 8 out of 10 pregnant women with preeclampsia, reducing their blood pressure from an average of 162/102 mmHg to 142/89 mmHg.

The treatment also significantly increased platelet counts in all participants, suggesting that nifedipine may help reverse thrombocytopenia associated with preeclampsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nifedipine and platelets in preeclampsia. Rubin, PC., Butters, L., McCabe, R.[2019]

In a study of 50 pregnant women with severe pre-eclampsia, long-term treatment with nicardipine effectively reduced both systolic and diastolic blood pressure across all treatment durations (short-term, medium-term, and long-term).

There were no adverse effects reported for mothers or their fetuses/newborns, indicating that long-term nicardipine treatment is safe and as effective as shorter treatment durations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term treatment with nicardipine for severe pre-eclampsia. Seki, H., Takeda, S., Kinoshita, K.[2019]

Oral nifedipine effectively lowers blood pressure in severely preeclamptic patients during hypertensive emergencies, with significant reductions in mean arterial pressure observed over time in a study of 10 patients.

The treatment resulted in an increase in cardiac index without significantly affecting heart rate or stroke index, indicating a favorable hemodynamic profile during the management of hypertension in preeclampsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic effects of oral nifedipine in preeclamptic hypertensive emergencies. Scardo, JA., Vermillion, ST., Hogg, BB., et al.[2019]

Nifedipine is more effective than other antihypertensives in controlling blood pressure in pregnant women with severe preeclampsia, based on a meta-analysis of nine trials involving 764 women.

Nifedipine also helps prolong gestation without increasing the risk of neonatal respiratory distress syndrome or perinatal deaths, indicating it is a safe option for managing severe preeclampsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical efficacy and perinatal outcome of nifedipine for severe preeclampsia: meta-analysis]. Liu, QQ., Yu, YH., Gong, SP., et al.[2013]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK537052/

Nifedipine - StatPearls - NCBI Bookshelf Nifedipine is a dihydropyridine calcium channel blocker approved for the treatment of chronic stable angina and hypertension.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05096728

Nifedipine Dosing Daily vs Twice a Day for Pre-eclampsia ... 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10238817/

Effectiveness of nifedipine, labetalol, and hydralazine as ... The effectiveness of the drugs to achieve 20% reduction of MAP could be ranked as follows: nifedipine>labetalol>hydralazine (57.49%, 42.13%, and 40.87%, ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03595982

Is Procardia XL 60 mg Q Daily Equivalent to 30 ... Secondary outcome will be effective control of BP throughout the day (0h, 4h, 8h, 12h, 16h, 20h and 24h) defined as BPs below 160/105 as well as side effects of ...

5. e-century.us e-century.us/files/ajcd/14/6/ajcd0160710.pdf

Long-acting nifedipine in the management of essential ... SR nifedipine, at various doses, effectively low- ers supine systolic blood pressure over 24 hours in patients with essential hypertension.

6. preeclampsia.org preeclampsia.org/the-news/Research-Roundup/risk-of-postpartum-readmission-after-hypertensive-disorder-of-pregnancy-and-variation-by-discharge-antihypertensive-medication-prescription

Risk Of Postpartum Readmission After Hypertensive ... The findings revealed that 86% of patients who did not receive a prescription for an anti-hypertensive medication had a 2.5 % readmission rate.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/2316590/

The use of nifedipine during the postpartum period in ... A significant reduction in mean arterial pressure was also noted in the nifedipine group between 18 and 24 hours postpartum (93.9 versus 100.2 mm Hg; p less ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11982344/

Postpartum management of hypertensive disorders of ... In the postpartum period, it is recommended that providers initiate antihypertensive medication for BPs ≥140/90 mm Hg with algorithms for ...

9. newsroom.heart.org newsroom.heart.org/news/severe-preeclampsia-treated-safely-with-nifedipine-during-labor-and-delivery

Severe preeclampsia treated safely with nifedipine during ... Women treated with the medicine were less likely to experience dangerously high blood pressure that would require treatment with fast-acting ...