Blood Pressure Medication for Pregnant Women with Hypertension

(CHAP2 Trial)

Overseen By Jhana Plump

Age: Any Age

Sex: Female

Trial Phase: Phase 1

Sponsor: University of Alabama at Birmingham

Must not be taking: Antihypertensives

Disqualifiers: Chronic hypertension, Fetal demise, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: prenatal period until delivery

74 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how controlling blood pressure (BP) in pregnant women with mild hypertension affects the baby's birth weight. It tests whether maintaining BP below 130/80mmHg is more beneficial than the usual care, which only treats when BP reaches 140/90mmHg or higher. The trial includes two groups: one receives medication (Labetalol or Nifedipine) to lower BP, while the other receives usual care. It suits women pregnant with one baby, whose BP is between 130-139/80-89mmHg before 20 weeks of pregnancy, and who plan to deliver at UAB Hospital. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Will I have to stop taking my current medications?

The trial requires that participants are not currently using any antihypertensive medications, so you would need to stop taking them to be eligible.

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

Research shows that labetalol and nifedipine often treat high blood pressure during pregnancy. Studies have found these medications to be generally safe and well-tolerated.

For labetalol, many studies report no harmful effects on mothers or babies. It is widely recommended for managing high blood pressure in pregnancy, with very few negative outcomes for the mother, fetus, or newborn.

Nifedipine is also considered safe for pregnant women with high blood pressure. It effectively lowers blood pressure and is usually given in a long-lasting form to maintain control.

Both medications have been used for many years and are widely accepted as safe options for managing high blood pressure during pregnancy. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Labetalol and Nifedipine for managing blood pressure in pregnant women with hypertension because these medications offer a targeted approach. Unlike some standard treatments that might not be suitable during pregnancy, Labetalol and Nifedipine are known for their safety profiles in this population. Labetalol works by blocking certain receptors to lower blood pressure, while Nifedipine relaxes blood vessels, making it easier for blood to flow. This dual approach could potentially provide more effective blood pressure control during pregnancy without compromising safety.

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

This trial will compare the effectiveness of labetalol and nifedipine in controlling blood pressure in pregnant women with hypertension. Studies have shown that both medications effectively manage high blood pressure during pregnancy. Research indicates that labetalol is often the first choice for treating preeclampsia, a pregnancy complication marked by high blood pressure, as it reduces excess proteins in urine and lowers the risk of death around the time of birth. Nifedipine, however, is particularly effective at lowering blood pressure in severe cases. Both medications work equally well for mild long-term high blood pressure during pregnancy. Overall, these medications offer promising options for managing blood pressure in pregnant women. Participants in this trial will receive different treatments to evaluate these outcomes. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for pregnant individuals planning to deliver at UAB Hospital, with a healthy single baby and no fetal anomalies. They should have mild high blood pressure (130-139/80-89mmHg) recorded twice before 20 weeks of pregnancy and be receiving care at UAB prenatal clinics.

Inclusion Criteria

Blood pressures 130-139/80-89mmHg on two occasions at least 4 hours apart prior to 20 weeks gestation

Viable singleton gestation

Planning to deliver at UAB Hospital

Exclusion Criteria

Fetal demise diagnosed prior to enrollment

I choose not to be randomly assigned to a treatment group.

I have known genetic abnormalities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either active treatment to BP<130/80mmHg or usual care with treatment only if BPs ≥140/90mmHg

prenatal period until delivery

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of hypertensive disorders and maternal adverse cardiovascular outcomes

6 weeks postpartum

What Are the Treatments Tested in This Trial?

Interventions

• Labetalol
• Nifedipine

Trial Overview The CHAP2 study tests if treating stage 1 hypertension in pregnancy with Labetalol or Nifedipine to lower blood pressure below 130/80mmHg improves birthweight outcomes. Participants are randomly assigned to either active treatment or usual care where treatment starts only if BP rises above 140/90mmHg.

How Is the Trial Designed?

Group I: BP goal <130/80mmHg Experimental Treatment 1 Intervention

Group II: BP goal <140/90 (usual care) 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?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

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]

Mild to moderate hypertension affects 7-9% of pregnancies and can lead to serious health issues for both mothers and babies, highlighting the need for effective treatment options.

Oral labetalol and nifedipine are recommended as safe and effective antihypertensive agents for managing mild to moderate hypertension in pregnant women, although more research is needed on the pharmacokinetics of these medications during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of oral labetalol and nifedipine in mild to moderate hypertension in pregnancy. Clark, SM., Dunn, HE., Hankins, GD.[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]

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]

A systematic review of 30 pharmacokinetic studies on methyldopa, labetalol, and nifedipine during pregnancy found no evidence of fetal accumulation of these antihypertensive drugs, suggesting they are safe for use in pregnant women.

Despite their widespread use, the review highlights a significant lack of comprehensive studies on the pharmacokinetics of these medications during pregnancy, indicating a need for more research to optimize dosing and ensure effective treatment without side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of the most commonly used antihypertensive drugs throughout pregnancy methyldopa, labetalol, and nifedipine: a systematic review. van de Vusse, D., Mian, P., Schoenmakers, S., et al.[2022]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12539438/

Comparative Effectiveness and Safety of Labetalol Versus ... The primary composite effectiveness outcome occurred in 53% of individuals, with no difference between those dispensed nifedipine vs labetalol ( ...

2. journals.lww.com journals.lww.com/jpcs/fulltext/2022/08030/effect_of_labetalol_for_treating_patients_with.2.aspx

Effect of Labetalol for Treating Patients with Pregnancy ... From 28 studies, 11 (39.2%) studies reported that labetalol was the best and first-line drug for the treatment of preeclampsia and eclampsia as compared to ...

3. ahajournals.org ahajournals.org/doi/10.1161/HYPERTENSIONAHA.121.18415

Oral Antihypertensives for Nonsevere Pregnancy ... Labetalol is the only antihypertensive agent to decrease proteinuria and perinatal death, although 95% CI just exclude unity. There is no ...

4. jacc.org jacc.org/doi/abs/10.1016/j.jacadv.2025.102054

Comparative Effectiveness and Safety of Labetalol Versus ... Conclusions. This study suggests that labetalol and nifedipine have similar effectiveness and safety in treating chronic hypertension during pregnancy.

5. ginekologiaipoloznictwo.com ginekologiaipoloznictwo.com/articles/treatment-of-gestational-hypertension-with-oral-labetalol-and-methyldopa-in-iraqi-pregnant-women.pdf

treatment-of-gestational-hypertension-with-oral-labetalol- ... Conclusions: Treatment of pregnancy hypertensive disorders is correlated with decreased blood pressure levels and adverse effects. Keywords: ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK582779/

Labetalol - MotherToBaby | Fact Sheets - NCBI Bookshelf - NIH Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Information on the use of labetalol in pregnancy is ...

7. jacc.org jacc.org/doi/10.1016/j.jacadv.2025.102054

Comparative Effectiveness and Safety of Labetalol Versus ... This study suggests that labetalol and nifedipine have similar effectiveness and safety in treating chronic hypertension during pregnancy.

8. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.073302

Hypertension in Pregnancy and Postpartum Labetalol is commonly used to treat hypertension in pregnant and postpartum patients, but twice-daily or more frequent dosing is a major ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11504833/

Effectiveness and safety of intravenous labetalol in severe pre ... There were no adverse effects on the mother or on the fetus observed in its use. Women with severe PET/eclampsia present late, and diagnosis of ...