Antihypertensive Treatment for Postpartum Hypertension

(P-PAT Trial)

Overseen By Anna Palatnik, MD

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Medical College of Wisconsin

Disqualifiers: Chronic hypertension, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether taking blood pressure medication after childbirth can lower high blood pressure and reduce health problems for new mothers. It focuses on women who experienced preeclampsia, a pregnancy complication marked by high blood pressure, and examines if medications like labetalol or nifedipine can prevent hospital readmissions. Participants will be randomly assigned to either take the medication or receive standard care without it. Women who gave birth within the last four days and had preeclampsia during or immediately after pregnancy are ideal candidates, particularly if their blood pressure remains high. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both labetalol and nifedipine are generally safe for treating high blood pressure after childbirth. Labetalol has been used safely in women with severe preeclampsia (a type of high blood pressure during pregnancy) without harming mothers or babies. However, some studies suggest that labetalol might not lower blood pressure as effectively as nifedipine.

Nifedipine, in contrast, significantly reduces the risk of hospital readmission due to high blood pressure issues. Specifically, patients taking nifedipine had about half the rate of readmission compared to those taking labetalol.

Both medications have similar safety outcomes regarding babies being born smaller than expected for their age—13% for labetalol and 12% for nifedipine—indicating equal safety in this aspect.

In summary, both treatments are well-tolerated, but nifedipine might be more effective in preventing hospital return visits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using labetalol and nifedipine for postpartum hypertension because these medications offer flexibility and tailored treatment options. Labetalol is a beta-blocker that works by relaxing blood vessels and slowing heart rate, while nifedipine is a calcium channel blocker that helps relax and widen blood vessels. This dual approach allows for personalized treatment based on the patient's specific needs and potential allergies, which is a significant advantage over the more generalized standard treatments. Additionally, both drugs are known for their rapid onset of action, which can be crucial for managing hypertension quickly after childbirth.

What evidence suggests that this trial's treatments could be effective for postpartum hypertension?

In this trial, participants will receive either nifedipine or labetalol as part of the treatment arm. Research has shown that nifedipine can significantly reduce the chance of hospital readmission for high blood pressure after childbirth, lowering this risk by 65% compared to those not taking the medication. Labetalol is another option for treating high blood pressure after childbirth, but some studies suggest it might not be as effective as nifedipine. For instance, patients taking labetalol had a higher readmission rate of about 10.8% compared to those not taking any medication. Overall, both medications effectively manage high blood pressure after childbirth, but nifedipine might be slightly better at preventing hospital readmissions. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for women over 18 who were diagnosed with preeclampsia during or immediately after pregnancy and have high blood pressure postpartum. It's not for those with chronic hypertension, a late diagnosis of preeclampsia, or mostly normal blood pressures after delivery.

Inclusion Criteria

You gave birth within the last 96 hours.

I was diagnosed with preeclampsia during or right after my pregnancy.

More than 30% of your blood pressure readings after giving birth were high (systolic 140 or higher OR diastolic 90 or higher).

Exclusion Criteria

I started blood pressure medication after giving birth due to high readings.

I was diagnosed with preeclampsia after leaving the hospital from giving birth.

I have long-term high blood pressure and now also have preeclampsia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive antihypertensive medication postpartum, with specific medication prescribed based on allergies and clinical appropriateness

6 weeks

2 visits (in-person) at 7-10 days and 6 weeks postpartum

Follow-up

Participants are monitored for safety and effectiveness after treatment, including blood pressure checks and postpartum assessments

6 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Labetalol
• Nifedipine

Trial Overview

The study compares the effects of starting antihypertensive drugs (Labetalol or Nifedipine) right after childbirth versus standard care on reducing high blood pressure and related health issues in women with recent preeclampsia.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

The patients randomized to the treatment group will have an antihypertensive medication prescribed to them. The specific medication will be either labetalol or nifedipine based on allergies and clinically appropriateness of the medication. The patient will be instructed on the dosing, timing, and possible adverse effects.

Group II: No-treatment Active Control 1 Intervention

Labetalol is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Labetalol for:

• Hypertension
• Preeclampsia

Approved in United States as Labetalol for:

• Hypertension
• Preeclampsia

Approved in Canada as Labetalol for:

• Hypertension
• Preeclampsia

Approved in Japan as Labetalol for:

• Hypertension

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

Pregnant women experiencing acute-onset, severe hypertension require urgent treatment with antihypertensive medications, ideally within 30-60 minutes, to prevent serious complications like maternal stroke.

First-line treatments include intravenous labetalol and hydralazine, with immediate release oral nifedipine as a potential alternative when intravenous access is not available, highlighting the importance of prompt and effective management in hypertensive emergencies during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACOG Committee Opinion No. 767 Summary: Emergent Therapy for Acute-Onset, Severe Hypertension During Pregnancy and the Postpartum Period. [2019]

In a study of pregnant women with hypertensive disorders, those treated with labetalol had a higher rate of intrauterine growth restriction in infants compared to those treated with nifedipine (38.8% vs. 15.5%).

Labetalol was also associated with a higher rate of fetal heart rate abnormalities in women with gestational hypertension and mild preeclampsia, indicating potential risks to fetal well-being, while no significant differences in adverse side effects or neonatal malformations were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nifedipine versus labetalol in the treatment of hypertensive disorders of pregnancy. Giannubilo, SR., Bezzeccheri, V., Cecchi, S., et al.[2013]

In a study of 60 pregnant women with severe hypertension, both nicardipine and labetalol effectively lowered blood pressure by 20%, with success rates of 70% and 63% respectively, indicating both medications are viable options for treatment.

Nicardipine resulted in a greater reduction in systolic and diastolic blood pressure compared to labetalol, and both medications were well tolerated, with no cases of hypotension reported, although moderate tachycardia was noted with nicardipine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term treatment of severe hypertension of pregnancy: prospective comparison of nicardipine and labetalol. Elatrous, S., Nouira, S., Ouanes Besbes, L., et al.[2013]

In a study of 112 pregnant women with chronic hypertension, both labetalol and nifedipine effectively controlled blood pressure, with no significant difference in overall efficacy between the two medications.

Nifedipine was associated with a notable reduction in central aortic pressure, while labetalol showed a significant decrease in diastolic blood pressure specifically in non-black women, suggesting potential ethnic differences in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy: A Randomized Controlled Trial. Webster, LM., Myers, JE., Nelson-Piercy, C., et al.[2022]

In a study of 124 postpartum women, both oral Labetalol and oral long-acting Nifedipine effectively managed hypertension, but Nifedipine achieved blood pressure control faster, averaging 30.4 hours compared to 35.6 hours for Labetalol.

While both medications were well tolerated, minor side effects were more common in the Nifedipine group, suggesting that while it may be more effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral labetalol versus oral nifedipine for the management of postpartum hypertension a randomized control trial. Ainuddin, J., Javed, F., Kazi, S.[2023]

In a study of 120 pregnant women with severe hypertension, oral nifedipine was found to reduce blood pressure more quickly than intravenous labetalol, taking an average of 27.25 minutes compared to 36.75 minutes for labetalol.

Nifedipine also required significantly fewer doses to achieve the target blood pressure, making it a potentially more convenient and effective option for managing severe hypertension in pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IV labetalol and oral nifedipine in acute control of severe hypertension in pregnancy-A randomized controlled trial. Zulfeen, M., Tatapudi, R., Sowjanya, R.[2019]

Pregnant women require different blood pressure targets and medications compared to nonpregnant individuals, with specific antihypertensive drugs like methyldopa, labetalol, and nifedipine being considered safe during pregnancy.

Certain medications, such as angiotensin converting enzyme inhibitors and angiotensin receptor blockers, should be avoided in pregnant women due to safety concerns, highlighting the importance of tailored treatment approaches for hypertension in pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antihypertensive drugs in pregnancy. Podymow, T., August, P.[2011]

In a randomized controlled trial involving 50 women with persistent postpartum hypertension, both oral labetalol and oral extended release nifedipine were effective in managing blood pressure, taking a similar amount of time to achieve control (approximately 37.6 hours for labetalol and 38.2 hours for nifedipine).

Labetalol was more effective at achieving blood pressure control with the initial starting dose compared to nifedipine (76% vs. 46%), and it also had fewer minor side effects (20% vs. 48%), making it a safer option for postpartum hypertension management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral labetalol compared to oral nifedipine for postpartum hypertension: A randomized controlled trial. Sharma, KJ., Greene, N., Kilpatrick, SJ.[2022]

In a study of 130 women with postpartum hypertension, oral Amlodipine (AML) achieved sustained blood pressure control faster than oral Labetalol (LAB), with a mean difference of 7.2 hours, indicating AML may be more effective for immediate management.

While AML resulted in fewer severe hypertensive episodes compared to LAB, a higher percentage of women in the AML group continued to need antihypertensives at discharge (55.4% vs. 32.3%), suggesting that while AML is effective initially, it may not provide long-term control as well as LAB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the efficacy of oral labetalol with oral amlodipine in achieving blood pressure control in women with postpartum hypertension: randomized controlled trial (HIPPO study-Hypertension In Pregnancy & Postpartum Oral-antihypertensive therapy). Gupta, A., Nayak, D., Sharma, J., et al.[2023]

Nicardipine and labetalol have similar success rates in controlling severe hypertension during pregnancy, based on a nested case control study and meta-analysis of existing data.

While nicardipine is effective, it is associated with more maternal side effects like tachycardia, headache, and nausea, whereas labetalol is linked to more neonatal side effects, including hypotension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The optimal treatment of severe hypertension in pregnancy: update of the role of nicardipine. Nooij, LS., Visser, S., Meuleman, T., et al.[2019]

Pregnant women experiencing acute-onset, severe hypertension require urgent treatment with antihypertensive medications, ideally within 30-60 minutes, to prevent serious complications like maternal stroke.

First-line treatments include intravenous labetalol and hydralazine, with immediate release oral nifedipine as a potential alternative when intravenous access is not available, highlighting the importance of prompt and effective management in hypertensive emergencies during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Committee Opinion No. 692 Summary: Emergent Therapy for Acute-Onset, Severe Hypertension During Pregnancy and the Postpartum Period. [2018]

Citations

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The safety outcome of small for gestational age occurred in 13% in the labetalol group and 12% in the nifedipine group, with an adjusted RR of ...

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The results indicating an elevated risk associated with labetalol use were consistent in models that excluded patients with prepregnancy hypertension.