Losartan for Preeclampsia

(LIVE-PE Trial)

Overseen By Kaila Brustkern, BS

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: Anna Stanhewicz, PhD

Must not be taking: Statins, Antihypertensives

Disqualifiers: Skin diseases, Tobacco use, others

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether losartan, an angiotensin receptor blocker, can reduce long-term blood vessel damage in women who experienced preeclampsia during pregnancy. Preeclampsia can cause high blood pressure and other complications, increasing the risk of heart disease later in life. The study compares the effects of losartan with a placebo (a pill with no active medication) on blood vessel health and inflammation. Women who may qualify for this trial are those who had a preeclamptic pregnancy within the last two years and are using birth control. As an Early Phase 1 trial, this research focuses on understanding how losartan works in people, offering participants a chance to contribute to groundbreaking medical insights.

Will I have to stop taking my current medications?

If you are currently taking any antihypertensive (blood pressure-lowering) medications or statins (cholesterol-lowering drugs), you will need to stop taking them to participate in this trial.

Is there any evidence suggesting that losartan is likely to be safe for humans?

Previous studies have safely used losartan in over 3,300 adults to treat high blood pressure. Most people tolerate it well without serious side effects. However, it can sometimes raise potassium levels in the blood, leading to hyperkalemia, a potentially dangerous condition if not monitored. Therefore, checking potassium levels is important for those taking losartan.

Losartan is not recommended during pregnancy because it may harm the unborn baby. However, this study tests losartan on women who have already given birth and experienced preeclampsia. Preeclampsia is a condition where pregnant women have high blood pressure and signs of organ damage. The study aims to determine if losartan can improve long-term heart health after preeclampsia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for preeclampsia, such as blood pressure medications like labetalol or methyldopa, losartan potassium offers a unique approach by specifically targeting the angiotensin II receptor. This mechanism could potentially improve blood flow and reduce blood pressure more effectively. Researchers are excited because losartan might address underlying causes of preeclampsia rather than just managing symptoms, offering hope for a more comprehensive treatment.

What evidence suggests that losartan might be an effective treatment for preeclampsia?

Research has shown that losartan, a medication that blocks certain chemicals in the body, can improve blood vessel health in women who have had preeclampsia. In this trial, participants will receive either losartan or a placebo. Studies found that after six weeks of taking losartan, blood vessels widened more easily, indicating better blood flow. Specifically, losartan helped the blood vessels relax and function better by enhancing their ability to widen. These findings suggest that losartan might help repair blood vessel damage in women with a history of preeclampsia, potentially lowering their risk of future heart disease. ^{6 7 8 9 10}

Who Is on the Research Team?

Anna Stanhewicz, PhD

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

This trial is for post-partum women over 18 who had preeclampsia in their last pregnancy within the past 24 months. Participants must be using birth control and not planning to get pregnant soon. They can't join if they have allergies to study drugs, use tobacco, have liver or metabolic diseases including CKD, had high blood pressure before pregnancy, gestational diabetes, are currently pregnant or breastfeeding, have skin diseases or a BMI under 18.5.

Inclusion Criteria

I am a woman over 18 who had preeclampsia in my last pregnancy within the last 2 years.

Using an effective method of birth control and not planning to become pregnant in the next 6 months.

Exclusion Criteria

You have had diabetes during pregnancy in the past.

I am taking medication to lower my cholesterol.

You had high blood pressure before becoming pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Placebo

Participants receive a daily oral placebo tablet for 6 weeks to assess baseline vascular function and inflammatory response

6 weeks

1 visit (in-person) at the end of treatment

Treatment - Losartan

Participants receive a daily oral losartan potassium tablet (50mg/day) for 6 weeks to test improvement in vascular function

6 weeks

1 visit (in-person) at the end of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Losartan Potassium

Trial Overview The study tests whether Losartan Potassium improves vascular function in women who've experienced preeclampsia by comparing it with a placebo. It involves examining blood vessels in the skin and analyzing inflammatory responses after taking either the medication or placebo.

How Is the Trial Designed?

Group I: Losartan Experimental Treatment 1 Intervention

6 weeks of daily (50mg/day) oral losartan potassium tablet

Group II: Placebo Placebo Group 1 Intervention

6 weeks of daily oral placebo tablet

Losartan Potassium is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Cozaar for:

• Hypertension
• Heart failure
• Diabetic nephropathy
• Stroke prevention in hypertension and left ventricular hypertrophy

Approved in United States as Cozaar for:

• Hypertension
• Diabetic nephropathy
• Stroke prevention in hypertension and left ventricular hypertrophy

Approved in Canada as Cozaar for:

• Hypertension
• Heart failure
• Diabetic nephropathy

Approved in Japan as Cozaar for:

• Hypertension
• Heart failure

Approved in China as Cozaar for:

• Hypertension
• Diabetic nephropathy

Approved in Switzerland as Cozaar for:

• Hypertension
• Heart failure

Who Is Running the Clinical Trial?

Anna Stanhewicz, PhD

Lead Sponsor

Trials

12

Recruited

460+

Published Research Related to This Trial

A validated reversed-phase high-performance thin-layer chromatography method has been developed for testing losartan potassium in COZAAR tablets, demonstrating sensitivity and reliability.

This new method offers an effective alternative to traditional HPLC stability testing, potentially improving the quality control processes for losartan potassium formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of losartan and its degradates in COZAAR tablets by reversed-phase high-performance thin-layer chromatography. McCarthy, KE., Wang, Q., Tsai, EW., et al.[2019]

Losartan potassium is an effective antihypertensive medication that works by blocking the angiotensin II receptor, showing similar blood pressure-lowering effects to other standard treatments like enalapril and atenolol in patients with mild to moderate hypertension.

It has a favorable safety profile, with minimal side effects such as dizziness and a low incidence of cough compared to ACE inhibitors, making it suitable for long-term use, especially in patients who are intolerant to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Losartan potassium: a review of its pharmacology, clinical efficacy and tolerability in the management of hypertension. Goa, KL., Wagstaff, AJ.[2022]

Losartan potassium is an effective once-daily antihypertensive medication that works by blocking the action of angiotensin II at the AT1 receptor, with its active metabolite E-3174 contributing to its prolonged effects.

It is well tolerated with a lower withdrawal rate due to adverse effects compared to placebo, but further long-term studies are needed to fully understand its safety profile, especially regarding potential risks like angioedema and effects in patients with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A risk-benefit assessment of losartan potassium in the treatment of hypertension. Burrell, LM.[2018]

Losartan potassium, an angiotensin II receptor antagonist, shows significant haemodynamic benefits in patients with heart failure, based on extensive clinical trials.

The drug is well tolerated with a low incidence of adverse effects related to kidney function, making it a safe option for treating hypertension and heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Losartan in heart failure: preclinical experiences and initial clinical outcomes. Sweet, CS., Rucinska, EJ.[2019]

In a 12-week study involving 366 hypertensive patients, losartan significantly reduced both systolic and diastolic blood pressure compared to placebo, demonstrating its efficacy as an antihypertensive medication.

Losartan was well tolerated with a safety profile similar to placebo, and there was no evidence of rebound hypertension after stopping the medication, indicating it is a safe option for managing mild-to-moderate hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative antihypertensive effects of losartan 50 mg and losartan 50 mg titrated to 100 mg in patients with essential hypertension. Ikeda, LS., Harm, SC., Arcuri, KE., et al.[2019]

Losartan is an effective antihypertensive medication that works by blocking the type 1 angiotensin II receptor, showing similar efficacy to other common blood pressure medications like enalapril, felodipine, and atenolol in clinical trials involving approximately 3700 patients.

The safety profile of losartan is favorable, with a low incidence of adverse effects similar to placebo, and a lower withdrawal rate due to side effects compared to placebo, although dizziness was reported more frequently by patients taking losartan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of losartan. Goldberg, A., Sweet, C.[2013]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40077915/

Oral Losartan Treatment Improves Microvascular Endothelial ... Results: Losartan treatment increased endothelium- (P < 0.001) and NO-dependent (P < 0.016) vasodilation compared with placebo. Losartan ...

2. academic.oup.com academic.oup.com/ajh/article/38/7/459/8074215

Oral Losartan Treatment Improves Microvascular Endothelial ... The primary findings of this study are that 6 weeks of systemic AT1R inhibition with oral losartan treatment improved endothelium-dependent dilation, via ...

3. ahajournals.org ahajournals.org/doi/10.1161/hyp.80.suppl_1.P209

Abstract P209: Six Weeks Oral Losartan Treatment ... Abstract P209: Six Weeks Oral Losartan Treatment Improves Endothelium-dependent Dilation In Normotensive Women With A History Of Preeclampsia.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04632589

Losartan for Improved Vascular Endothelial Function After ... Women who develop preeclampsia during pregnancy are more likely to develop and die of cardiovascular disease later in life, even if they are otherwise healthy.

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

Effectiveness of antihypertensive therapies and maternal ... Effectiveness of antihypertensive therapies and maternal-neonatal outcomes in preeclampsia and eclampsia women: an analytical retrospective study from sudan.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/020386s062lbl.pdf

COZAAR® (losartan potassium) tablets - accessdata.fda.gov Coadministration of losartan with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients. Increases ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK526065/

Losartan - StatPearls - NCBI Bookshelf Safety, tolerability, and outcomes of losartan use in patients hospitalized with SARS-CoV-2 infection: A feasibility study. PLoS One. 2020 ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2010/020386s052lbl.pdf

cozaar® (losartan potassium tablets) use in pregnancy There are no data on the effect of Cozaar on ... Hypertension. Cozaar has been evaluated for safety in more than 3300 adult patients treated for essential.

9. ahajournals.org ahajournals.org/doi/10.1161/hypertensionaha.106.075895

Update on the Use of Antihypertensive Drugs in Pregnancy Of note, with antihypertensive treatment, there seems to be less risk of developing severe hypertension (risk ratio: 0.50, with a number needed to treat of 10) ...

10. reference.medscape.com reference.medscape.com/drug/cozaar-arbli-losartan-342323

Cozaar, Arbli (losartan) dosing, indications, interactions, ... losartan and potassium chloride both increase serum potassium. Use Caution ... Risk of fetal compromise if given during pregnancy. resmetirom. losartan ...