Antihypertensive Therapy for Preeclampsia

(Achieve Trial)

Recruiting at 1 trial location

Overseen By Alan Tita, MD

Age: < 65

Sex: Female

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Disqualifiers: Severe preeclampsia, Renal dysfunction, Stage 2 hypertension, 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: Unknown

Duration: Up to 14 weeks

132 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if lowering blood pressure to less than 140/90 mmHg in pregnant women with high blood pressure can help prolong pregnancy. Participants will receive either regular care, where treatment begins if blood pressure reaches 160/110 mmHg or higher, or an experimental approach with more proactive antihypertensive treatment (blood pressure medications). It suits pregnant women between 23 and 36 weeks who have high blood pressure without severe complications and plan to continue their pregnancy. As an unphased trial, this study allows participants to contribute to important research that could improve pregnancy outcomes for many women.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should not have contraindications to labetalol and nifedipine XL, which are common blood pressure medications.

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

Research has shown that blood pressure medications during pregnancy are generally safe for both mothers and babies. One study found that treating mild high blood pressure in pregnant women led to better health outcomes without major safety issues. Another analysis found that medications like labetalol and nifedipine can help lower the risk of preeclampsia, a pregnancy complication with high blood pressure, and early birth. While no treatment is completely without risk, these findings suggest that blood pressure medications are well-tolerated and help manage blood pressure during pregnancy. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a more proactive approach to managing blood pressure in preeclampsia. Typically, antihypertensive treatments for preeclampsia are only initiated when blood pressure hits a high threshold of 160/110 mmHg. This trial, however, examines the effects of starting treatment earlier, aiming for a blood pressure goal of less than 140/90 mmHg. By potentially reducing the risks associated with high blood pressure earlier, this approach could offer better outcomes for both mothers and babies.

What evidence suggests that antihypertensive treatment might be effective for preeclampsia?

This trial will compare two approaches to antihypertensive treatment for preeclampsia. Research has shown that blood pressure medications can help manage high blood pressure in pregnant women with preeclampsia. One study found that hydralazine effectively controlled blood pressure in these cases. Another study showed that treating mild high blood pressure during pregnancy can improve health outcomes for both mothers and babies. Additionally, common blood pressure medications like labetalol and nifedipine have been shown to lower the risk of developing preeclampsia and experiencing preterm birth. These findings suggest that blood pressure treatments are important for managing preeclampsia and safely extending pregnancy. ^{1 3 5 6 7}

Who Is on the Research Team?

Rachel Sinkey, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

The ACHIEVE Trial is for pregnant women with high blood pressure disorders, including gestational hypertension or non-severe preeclampsia. Eligible participants are those between 23 and 35+6 weeks of pregnancy, expecting a single baby or twins, without severe preeclampsia or other complications that require immediate delivery.

Inclusion Criteria

Prenatal care or healthcare visit with documented blood pressure at less than 21 weeks gestation

You are not showing signs of severe preeclampsia or need to deliver the baby right away when you join the study.

You are pregnant with one baby or with twins, and your pregnancy is at least 14 weeks along.

Exclusion Criteria

I cannot take labetalol or nifedipine XL due to adverse reactions.

Your baby is smaller than most babies at the time of enrollment.

I have new headaches or vision problems that medication doesn't help.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive antihypertensive treatment to maintain blood pressure below 140/90 mmHg

Up to 14 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Antihypertensive treatment

Trial Overview This trial tests if lowering blood pressure below 140/90 mmHg in pregnant women with hypertension can extend the duration of their pregnancy. It's a randomized study where some will receive antihypertensive treatment to achieve this target.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

Antihypertensive treatment for a BP goal of less than 140/90 mmHg

Group II: Usual Care Active Control 1 Intervention

Antihypertensive treatment only if BP ≥ 160/110 mmHg

Antihypertensive treatment is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Antihypertensive medications for:

• Hypertension in pregnancy
• Preeclampsia

Approved in United States as Antihypertensive medications for:

• Hypertension in pregnancy
• Preeclampsia
• Chronic hypertension

Approved in Canada as Antihypertensive medications for:

• Hypertension in pregnancy
• Preeclampsia

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Mild chronic hypertension in pregnancy generally has a better prognosis than preeclampsia, and while antihypertensive therapy is recommended for severe cases, it may not significantly improve outcomes in mild cases.

Alpha-methyl-dopa is the preferred initial oral antihypertensive medication during pregnancy, as it has not shown adverse short-term or long-term effects on the fetus or neonate, making it a safe option for managing high blood pressure in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of hypertensive diseases in pregnancy--general recommendations and long-term oral therapy]. Rath, W.[2013]

Recent studies have shown promising results in screening for preeclampsia before symptoms appear, which could improve early detection and management of hypertension during pregnancy.

While first-line medications for treating hypertensive complications of preeclampsia remain largely unchanged due to their established safety and efficacy, new second-line drugs have demonstrated effectiveness and safety, but further long-term studies are needed to determine if they can replace current standards.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathophysiology and medical management of systemic hypertension in preeclampsia. Frishman, WH., Veresh, M., Schlocker, SJ., et al.[2019]

Severe hypertension in pregnancy (systolic BP ≥160 mmHg or diastolic BP ≥110 mmHg) should be treated with antihypertensive therapy to reduce the risk of serious complications, with parenteral hydralazine and labetalol being the most supported options.

There is no clear consensus on treating non-severe hypertension (systolic BP 140-159 mmHg or diastolic BP 90-109 mmHg) due to insufficient evidence from trials, and while treatment may lower high BP, it could also negatively impact fetal growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to manage hypertension in pregnancy effectively. Magee, LA., Abalos, E., von Dadelszen, P., et al.[2023]

In a study of 440 preeclampsia patients, the use of blood pressure medication did not significantly affect the likelihood of hospital readmission, suggesting that medication alone may not be a determining factor.

However, patients on low doses of blood pressure medication had a significantly higher risk of readmission, indicating that clinicians should be cautious about prescribing lower doses to avoid potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood pressure medication use and postpartum hospital readmission among preeclampsia patients. Gesner, T., Fogel, J., Bryson, L.[2023]

Magnesium sulfate is the preferred treatment for preventing and controlling seizures in severe preeclampsia, significantly reducing the risk of eclampsia by 58% compared to placebo.

Other antihypertensive medications, such as intravenous hydralazine and labetalol, can be used to manage high blood pressure in preeclamptic patients, with labetalol being favored for its lower risk of causing reflex tachycardia and hypotension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapeutic options for the treatment of preeclampsia. McCoy, S., Baldwin, K.[2019]

Preeclampsia is a serious pregnancy complication that poses significant risks to both mothers and their babies, but currently, there are no effective biomarkers or preventive strategies available for clinical use.

Common medications for managing hypertension during pregnancy include methyldopa and labetalol, with higher blood pressure thresholds for starting treatment compared to non-pregnant patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypertension in pregnancy. Solomon, CG., Seely, EW.[2011]

Hypertension occurs in about 10% of pregnancies and can pose serious risks to both mothers and babies, making careful management essential.

Safe antihypertensive medications during pregnancy include labetalol, nifedipine, and methyldopa, while certain drugs like ACE inhibitors and diuretics should be avoided due to potential harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hypertension in pregnancy]. Clivaz Mariotti, L., Saudan, P., Landau Cahana, R., et al.[2007]

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]

Hypertensive disorders affect about 10% of pregnancies, with careful monitoring significantly reducing neonatal mortality, highlighting the importance of identifying women at risk for preeclampsia for better management.

Prophylactic low-dose aspirin may help prevent preeclampsia, but its effectiveness in reducing severe cases and improving outcomes is still uncertain; current treatments for hypertension in pregnancy include hydralazine, labetalol, and methyldopa, while magnesium sulfate is crucial for managing preeclampsia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hypertension and its treatment in pregnancy]. Jerie, P.[2006]

Hypertensive disorders in pregnancy, particularly pre-eclampsia, are a leading cause of maternal mortality, especially in Brazil, highlighting the need for effective management strategies.

The best treatment for pre-eclampsia is often early delivery, and magnesium sulfate is recommended to prevent seizures in severe cases, while medications like hydralazine, nifedipine, and labetalol are used to manage hypertensive crises.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pre-eclampsia treatment according to scientific evidence]. Noronha Neto, C., de Souza, AS., Amorim, MM.[2011]

Recent clinical trials have shown that second-line medications for treating hypertensive disorders in pregnancy are both effective and safe, but more long-term studies are needed to determine if they can replace current standard treatments.

Despite some advancements in understanding hypertension in pregnancy, first-line drug therapies remain largely unchanged due to their extensive research backing, particularly for conditions like preeclampsia and chronic hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic approaches for the management of systemic hypertension in pregnancy. Awad, K., Ali, P., Frishman, WH., et al.[2005]

Citations

1. ajogmfm.org ajogmfm.org/article/S2589-9333(24)00094-6/fulltext

The “Preeclampsia and Hypertension Target Treatment ... A multicenter prospective study to evaluate the effectiveness of the antihypertensive therapy based on maternal hemodynamic findings.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10189071/

An updated meta‐analysis of randomized controlled trials This meta‐analysis aimed to clarify if active treatment of mild hypertension during pregnancy results in better maternal and fetal outcomes.

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

Hypertension in Pregnancy and Postpartum In addition, recent data suggest that labetalol may be less effective in the postpartum period compared with calcium channel blockers and may be ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12517578/

Effectiveness of antihypertensive therapies and maternal ... Conclusions: Hydralazine was the most effective antihypertensive medication for controlling blood pressure in the management of PE/E, with combination therapies ...

5. ajog.org ajog.org/article/S0002-9378(25)00218-2/fulltext

Oral antihypertensive treatment during pregnancy In the network meta-analysis, labetalol vs nifedipine was associated with a reduction in preeclampsia (relative risk, 0.50 [0.28–0.87]; 15 studies) and preterm ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa2201295

Treatment for Mild Chronic Hypertension during Pregnancy To evaluate the benefits and safety of pharmacologic antihypertensive therapy during pregnancy, we designed a randomized trial involving women ...

7. dig.pharmacy.uic.edu dig.pharmacy.uic.edu/faqs/2022-2/october-2022-faqs/what-data-support-initiation-of-antihypertensive-therapy-for-mild-chronic-hypertension-in-pregnancy/

What data support initiation of antihypertensive therapy for ... Meta-analyses also did not find improved outcomes other than a reduction in severe hypertension with use of antihypertensives for mild chronic hypertension in ...