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

Trial Summary

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.

What data supports the effectiveness of the drugs labetalol and nifedipine for treating high blood pressure in pregnant women?

Research shows that both labetalol and nifedipine effectively control blood pressure in pregnant women with chronic hypertension, with similar outcomes in reducing blood pressure levels. They are considered safe options for managing high blood pressure during pregnancy. ^{1 2 3 4 5}

Is blood pressure medication safe for pregnant women with hypertension?

Research shows that both labetalol and nifedipine are generally safe for managing high blood pressure in pregnant women, with studies comparing their effects and side effects. These medications help control blood pressure without significant differences in safety outcomes for mothers and babies. ^{1 3 4 6 7}

How does the drug combination of labetalol and nifedipine differ from other treatments for hypertension in pregnancy?

Labetalol and nifedipine are both considered safe for treating high blood pressure in pregnant women, with labetalol typically given intravenously for severe cases and nifedipine taken orally. This combination is unique because it offers flexibility in administration routes and is supported by evidence for managing both mild to moderate and severe hypertension during pregnancy. ^{1 2 3 5 8}

What is the purpose of this trial?

The CHAP2 study is designed to provide preliminary data for a larger multicenter study to assess whether treatment of stage 1 hypertension (HTN) in pregnancy improves maternal and or neonatal outcomes. The primary objective of this pilot study is to determine if anti-HTN treatment to BP\<130/80mmHg in pregnant patients with stage 1 HTN is associated with a difference in birthweight percentile at delivery. Patients with stage 1 hypertension in pregnancy will be randomized to BP goals of \<130/80mmHg or usual care to treatment only if BPs ≥140/90mmHg. For this pilot, the investigator will randomize a total of 74 eligible participants, 37 to active treatment to BP\<130/80mmHg and 37 to usual care.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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 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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

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

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

Antihypertensive drugs in pregnancy. [2011]

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

Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy: 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. United States pubmed.ncbi.nlm.nih.gov

A review of oral labetalol and nifedipine in mild to moderate hypertension in pregnancy. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

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

8. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of the most commonly used antihypertensive drugs throughout pregnancy methyldopa, labetalol, and nifedipine: a systematic review. [2022]