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

20 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Losartan for treating preeclampsia?

Losartan is known to effectively lower high blood pressure, as shown in studies where it reduced blood pressure in patients with hypertension (high blood pressure). While preeclampsia involves high blood pressure during pregnancy, the effectiveness of Losartan specifically for preeclampsia is not directly addressed in the provided research. ^{1 2 3 4 5}

How does the drug Losartan Potassium differ from other treatments for preeclampsia?

Losartan Potassium is unique because it is an angiotensin II receptor blocker, which means it works by blocking a specific chemical in the body that causes blood vessels to tighten, helping to lower blood pressure. This mechanism is different from other treatments for preeclampsia, which may not specifically target this pathway. ^{1 2 4 5 6}

What is the purpose of this trial?

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. The reason why this occurs is unclear but may be related to blood vessel damage and increased inflammation that occurs during the preeclamptic pregnancy and persists postpartum. The purpose of this investigation is to determine the mechanisms contributing to this lasting blood vessel damage and to test whether taking a medication that blocks angiotensin II receptors (losartan) decrease these negative effects in women who have had preeclampsia. Identification of these mechanisms and treatment strategies may lead to better clinical management,of cardiovascular disease risk in these women. In this study we use the blood vessels in the skin as a representative vascular bed. Using a minimally invasive technique (intradermal microdialysis for the local delivery of pharmaceutical agents) we examine the blood vessels in a nickle-sized area of the skin in women who have had preeclampsia. We make these measurements after the subjects take a placebo and after they take losartan (an angiotensin II receptor blocker) to test whether this treatment improves vascular function in these women. As a compliment to these measurements, we also draw blood from the subjects and isolate the inflammatory cells to test how sensitive their inflammatory responses are following the placebo and the losartan treatment.

Research Team

Anna Stanhewicz, PhD

Principal Investigator

University of Iowa

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Determination of losartan and its degradates in COZAAR tablets by reversed-phase high-performance thin-layer chromatography. [2019]

2. England 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. [2019]

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

Losartan in heart failure: preclinical experiences and initial clinical outcomes. [2019]

4. New Zealand pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of losartan. [2013]

6. New Zealand pubmed.ncbi.nlm.nih.gov

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