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

300 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drugs Labetalol and Nifedipine for treating postpartum hypertension?

Research shows that both Labetalol and Nifedipine effectively control blood pressure in pregnant women with chronic hypertension, with similar outcomes in mean blood pressure levels. Additionally, Labetalol may offer a slight advantage in reducing diastolic blood pressure in non-black women compared to Nifedipine. ^{1 2 3 4 5}

Is the treatment for postpartum hypertension safe?

Labetalol and nifedipine are considered safe for use in pregnancy and postpartum hypertension, as they have been studied for managing high blood pressure in pregnant women. These medications are generally well-tolerated and are commonly used to control severe hypertension during and after pregnancy. ^{2 4 5 6 7}

How does the drug Labetalol differ from Nifedipine for postpartum hypertension?

Labetalol and Nifedipine are both used to manage postpartum hypertension, but they work differently. Labetalol is a beta-blocker that helps slow the heart rate, while Nifedipine is a calcium channel blocker that relaxes blood vessels. Studies suggest that Nifedipine may control blood pressure faster, but Labetalol might be needed less often after discharge. ^{3 8 9 10 11}

What is the purpose of this trial?

The goal of this study is to compare whether antihypertensive treatment in the postpartum period decreases postpartum hypertension and its associated maternal morbidity, including risk of readmission and healthcare utilization in comparison with no treatment. Women with preeclampsia diagnosed during the antepartum, intrapartum or postpartum period will be randomized to either initiate antihypertensive treatment or standard of care. We hypothesize that postpartum antihypertensive treatment of patients with preeclampsia will decrease risk of hospital readmission, healthcare utilization and the number of severe range blood pressures at postpartum follow-up visits.

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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 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 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 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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy: A Randomized Controlled Trial. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

IV labetalol and oral nifedipine in acute control of severe hypertension in pregnancy-A randomized controlled trial. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Oral labetalol compared to oral nifedipine for postpartum hypertension: A randomized controlled trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Short-term treatment of severe hypertension of pregnancy: prospective comparison of nicardipine and labetalol. [2013]

5. Netherlands pubmed.ncbi.nlm.nih.gov

The optimal treatment of severe hypertension in pregnancy: update of the role of nicardipine. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Antihypertensive drugs in pregnancy. [2011]

7. Germany pubmed.ncbi.nlm.nih.gov

Nifedipine versus labetalol in the treatment of hypertensive disorders of pregnancy. [2013]

8. Pakistan pubmed.ncbi.nlm.nih.gov

Oral labetalol versus oral nifedipine for the management of postpartum hypertension a randomized control trial. [2023]

9. England 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). [2023]

10. United States pubmed.ncbi.nlm.nih.gov

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

11. United States 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]