Furosemide for High Blood Pressure

Overseen By Annet Kirabo, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Vanderbilt University Medical Center

Must be taking: Antihypertensives

Disqualifiers: Diabetes, Autoimmune disease, Recent vaccination, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Furosemide, a diuretic or water pill, can aid individuals with salt-sensitive high blood pressure—a condition where blood pressure rises with excessive salt intake. Researchers aim to understand how certain immune cells, called monocytes, respond to salt and their potential link to high blood pressure. Participants will follow a special diet and take Furosemide to observe its effects on blood pressure. Individuals diagnosed with high blood pressure who are not overweight might be suitable for this study. As a Phase 1 and Phase 2 trial, this research focuses on understanding Furosemide's mechanism in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that participants with blood pressure below certain levels after stopping therapy are excluded, which suggests that some medication adjustments might be necessary.

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

Research has shown that furosemide effectively treats high blood pressure and fluid buildup in conditions like heart failure. As a strong diuretic, it helps the body remove excess water and salt. However, this can sometimes lead to dehydration or an imbalance in electrolytes, which are minerals in the blood that help control important body functions.

Some studies have found that furosemide can cause blood pressure to drop too low, especially if the body loses too much water, potentially causing dizziness or lightheadedness. Doctors must monitor these effects, particularly during a clinical trial.

Despite these concerns, furosemide is commonly used and has received FDA approval for treating high blood pressure and other conditions. This approval suggests that, when used correctly, it is generally considered safe. However, like all medications, it may have side effects that require management. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about furosemide for high blood pressure because it targets the body's salt and water balance in a unique way. Unlike standard treatments that typically focus on relaxing blood vessels or blocking certain hormones, furosemide is a diuretic that helps the body expel excess salt and water, which can lower blood pressure quickly. This approach not only offers a different mechanism of action but also the potential for rapid results, making it an appealing option for those who need immediate blood pressure reduction.

What evidence suggests that Furosemide might be an effective treatment for high blood pressure?

Research has shown that furosemide, a type of water pill, can lower blood pressure. On average, it reduces systolic pressure by about 8 points and diastolic pressure by about 4 points. This medication already treats high blood pressure and swelling from heart and kidney issues. In this trial, participants will follow the Weinberger protocol, which includes administering 40 mg of furosemide or Lasix orally. Previous studies, including one with women, showed that furosemide lowered high blood pressure in 60% of participants after just one week. These findings suggest that furosemide could help manage high blood pressure, even for those sensitive to salt. ^{4 5 6 7 8}

Who Is on the Research Team?

Annet Kirabo

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with a healthy BMI (18.5-24.9) who have high blood pressure, either newly diagnosed or existing, and are currently on medication or have blood pressure above certain levels. It's not open to those with diabetes, recent vaccinations, pregnancy, substance abuse issues, metal implants, autoimmune diseases, claustrophobia that prevents MRI scans or those who've had a recent heart event.

Inclusion Criteria

Only subjects who give informed consent will be studied

You have a healthy body weight for your height.

I have high blood pressure or am on medication for it.

Exclusion Criteria

You are currently using a lot of alcohol or illegal drugs.

I understand and can follow the study's requirements.

I have diabetes, either type 1 or 2.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Washout

Participants undergo a washout period to eliminate the effects of medications

2 weeks

Home monitoring or interim scheduled visits

Salt Loading

Participants undergo salt loading with a high-salt diet and saline infusion

1 day

Inpatient stay

Salt Depletion

Participants undergo salt depletion with a low-salt diet and furosemide administration

1 day

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after the protocol

1 day

Discharge with instructions

What Are the Treatments Tested in This Trial?

Interventions

• Furosemide 40 mg

Trial Overview The study tests if the drug Furosemide at 40 mg can be used as an indicator of salt-sensitivity in people with high blood pressure by observing immune cell activation. The goal is to see if this response correlates with hypertension due to salt intake.

How Is the Trial Designed?

Group I: Weinberger protocol Experimental Treatment 1 Intervention

During the Weinberger protocol, salt loading will be achieved by the combination of a high-salt diet (isocaloric, 160 mEq Na and 70 mEq K), and an infusion of 2L of saline (300 mEq Na+). Patients will have free access to water but their food will be limited to that provided by the protocol. Salt depletion will be accomplished by administering an isocaloric diet containing 10 mEq Na and 70 mEq K and continued unlimited water intake. At 8 am, 12 noon and 4 pm, subjects will be given 40 mg of furosemide or lasix orally.

Furosemide 40 mg is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Lasix for:

• Edema
• Hypertension
• Hypercalcemia
• Nephrotic syndrome

Approved in European Union as Lasix for:

• Oedema
• Hypertension
• Hypercalcaemia

Approved in Canada as Frusemide for:

• Edema
• Hypertension

Approved in Japan as Lasix for:

• Edema
• Hypertension
• Cirrhosis

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

In a study of 818 elderly patients (75 years and older) admitted to a geriatric unit, 32.6% were prescribed furosemide, highlighting its widespread use in this population.

Alarmingly, 69.2% of these furosemide prescriptions were found to be outside established guidelines, indicating a significant risk of misuse and lack of medical re-evaluation for ongoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of the prescription of furosemide in persons aged 75years and older in a geriatric acute-care unit]. Buttard, M., Putot, A., d'Athis, P., et al.[2019]

In a study of 17,068 hospitalized patients, 13.9% received furosemide, primarily for congestive heart failure, indicating its common use in managing cardiovascular conditions.

While 10.1% of furosemide recipients experienced adverse reactions, serious life-threatening effects were rare, suggesting that furosemide is generally safe, especially when potassium supplements are used to mitigate hypokalemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical toxicity of furosemide in hospitalized patients. A report from the Boston Collaborative Drug Surveillance Program. Greenblatt, DJ., Duhme, DW., Allen, MD., et al.[2019]

In a study involving five patients with congestive heart failure, the two proprietary preparations of frusemide (Lasix and Urex) showed no significant differences in their effectiveness.

Both preparations were equally effective in alleviating symptoms and in biochemical test results, indicating that either option can be used without concern for differing efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of two proprietary preparations of frusemide in patients with congestive heart failure. Pan, HY., Wang, RY., Chan, TK.[2021]

A study comparing 40 mg tablets of Frusid and Lasix formulations of frusemide in healthy volunteers found no significant differences in urinary volume or electrolyte content (Na+, K+, Cl-) after administration.

The results indicate that both formulations have equivalent bioavailability, meaning they are equally effective in their diuretic action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability of two preparations of frusemide. Paton, DM.[2013]

In a double-blind crossover study involving hypertensive patients, both furosemide and hydrochlorothiazide effectively reduced blood pressure over three months, but hydrochlorothiazide showed a greater reduction, particularly in systolic blood pressure.

The enhanced effectiveness of hydrochlorothiazide may be due to its longer duration of action, which allows for a more continuous diuretic effect and better maintenance of reduced extracellular fluid volume throughout the day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Furosemide compared with hydrochlorothiazide. Long-term treatment of hypertension. Araoye, MA., Chang, MY., Khatri, IM., et al.[2016]

A study involving 24 healthy male volunteers demonstrated that Salurin and Lasix, both 40 mg furosemide tablets, are bioequivalent, meaning they have similar absorption and effectiveness in the body.

The bioequivalence was confirmed through pharmacokinetic analysis, with key parameters showing no significant differences and falling within the FDA's accepted range, indicating that Salurin can be used interchangeably with Lasix.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence evaluation of two brands of furosemide 40 mg tablets (Salurin and Lasix) in healthy human volunteers. Najib, N., Idkaidek, N., Beshtawi, M., et al.[2013]

In a study of 115 elderly patients (average age 72) with hypertension or heart failure, the new slow-release formulation of furosemide (Lasix Retard) significantly improved clinical conditions in 34 out of 52 heart failure patients and reduced blood pressure from 187/99 to 166/93 after one year.

Lasix Retard effectively replaced thiazide diuretics without causing significant changes in blood pressure or metabolic indicators, and its side effects were comparable to those of thiazide diuretics, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Furosemide capsules in the treatment of hypertension or heart failure in the elderly in general practice]. Terland, O.[2013]

The slow-release formulation of furosemide (Eutensin) showed a 42% lower area under the curve (AUC0-24) compared to conventional furosemide tablets (Lasix), indicating a slower absorption and prolonged action.

While the slow-release furosemide resulted in less immediate diuretic effect (lower urine volume and sodium/chloride excretion in the first 10 hours), it may be beneficial for treating hypertension due to its sustained release and prolonged duration of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic and pharmacokinetic study of a slow-release formulation of furosemide in man. Ebihara, A., Tawara, K., Oka, T.[2013]

In a study of 64 patients with mild to moderate essential hypertension, 30 mg/day of slow-release frusemide for 12 months significantly lowered blood pressure and had a comparable antihypertensive effect to thiazide diuretics.

Frusemide also resulted in improved metabolic profiles by reducing fasting serum glucose, hemoglobin A1c, albumin, and serum calcium, while increasing serum sodium and chloride, suggesting it has fewer metabolic side effects than thiazides.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term treatment with slow-release frusemide compared with thiazide treatment in arterial hypertension. Jørgensen, H., Anderssen, N., Silsand, T., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7156893/

Blood pressure‐lowering efficacy of loop diuretics for primary ... The blood pressure‐lowering effect was modest, with systolic pressure lowered by 8 mmHg and diastolic pressure by 4 mmHg.

2. sciencedirect.com sciencedirect.com/science/article/pii/S1889183724000540

Diuretics use in the management of hypertension The patients exhibited a dose-dependent decrease in blood pressure and the difference of those treated with 1 and 2 mg compared to those treated with placebo ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2012/016273s066lbl.pdf

LASIX (furosemide) Tablets 20, 40, and 80 mg WARNING ... Hypertensive patients should avoid medications that may increase blood pressure, including over-the-counter products for appetite suppression and cold symptoms.

4. go.drugbank.com go.drugbank.com/drugs/DB00695

Furosemide: Uses, Interactions, Mechanism of Action Furosemide is a loop diuretic used to treat hypertension and edema in congestive heart failure, liver cirrhosis, renal disease, and hypertension.

5. ahajournals.org ahajournals.org/doi/10.1161/HYPERTENSIONAHA.120.16133

Furosemide for Accelerated Recovery of Blood Pressure ... In women randomized to furosemide, there was a 60% reduction in the prevalence of persistently elevated blood pressure at 7 days when ...

6. mayoclinic.org mayoclinic.org/drugs-supplements/furosemide-oral-route/description/drg-20071281

Furosemide (oral route) - Side effects & dosage High blood pressure may also increase the risk of heart attacks. These problems may be less likely to occur if blood pressure is controlled.

7. webmd.com webmd.com/drugs/2/drug-5512-8043/furosemide-oral/furosemide-oral/details

Furosemide (Lasix) - Uses, Side Effects, and More Low Blood Pressure with Worsening Kidney Function. Water loss from furosemide can lower your blood pressure too much and cause dehydration.

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK499921/

Furosemide - StatPearls - NCBI Bookshelf A boxed warning suggests the cautious use of furosemide as it is a potent diuretic, which can predispose to excessive loss of water and electrolytes, resulting ...