Furosemide for High Blood Pressure

Recruiting in Palo Alto (17 mi)

Overseen by Annet Kirabo

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Vanderbilt University Medical Center

Must be taking: Antihypertensives

Disqualifiers: Diabetes, Autoimmune disease, Recent vaccination, others

No Placebo Group

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

Salt-sensitive hypertension affects nearly 50% of the hypertensive and 25% of the normotensive population, and strong evidence indicates that reducing salt intake decreases blood pressure and cardiovascular events. The precise mechanisms of how dietary salt contributes to blood pressure elevation, renal injury, and cardiovascular disease remains unclear. Our data indicated that monocytes exhibit salt sensitivity, and the investigators hypothesize that of salt sensitivity of these and similar immune cells correlate with the hypertensive response to salt intake. Currently, the research tools for diagnosing salt-sensitivity are costly, time consuming and laborious. In this study the investigators will identify monocyte salt-sensitivity as a marker of salt-sensitive hypertension.

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 furosemide generally safe for humans?

Furosemide is generally considered safe for humans, with serious side effects being uncommon. Common side effects include dehydration and low potassium levels, especially at higher doses, but these can be managed with supplements. ^{1 2 3 4 5}

How does the drug Furosemide differ from other treatments for high blood pressure?

Furosemide, especially in its slow-release form, is unique because it provides a prolonged diuretic effect, which helps in managing high blood pressure by reducing fluid volume in the body. Unlike some other diuretics, it has fewer metabolic side effects, making it a preferable option for long-term use in certain patients. ^{2 6 7 8 9}

Research Team

Annet Kirabo

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Furosemide 40 mg (Loop Diuretic)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Jeffrey R. Balser

Vanderbilt University Medical Center

Chief Executive Officer since 2009

MD and PhD from Vanderbilt University

Rick W. Wright

Vanderbilt University Medical Center

Chief Medical Officer since 2023

MD from University of Missouri-Columbia

Findings from Research

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 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]

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]

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]

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]

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]

References

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

Clinical toxicity of furosemide in hospitalized patients. A report from the Boston Collaborative Drug Surveillance Program. [2019]

2. Norway pubmed.ncbi.nlm.nih.gov

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

3. Australia pubmed.ncbi.nlm.nih.gov

Efficacy of two proprietary preparations of frusemide in patients with congestive heart failure. [2021]

4. France pubmed.ncbi.nlm.nih.gov

[Evaluation of the prescription of furosemide in persons aged 75years and older in a geriatric acute-care unit]. [2019]

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

Bioequivalence evaluation of two brands of furosemide 40 mg tablets (Salurin and Lasix) in healthy human volunteers. [2013]

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

Bioavailability of two preparations of frusemide. [2013]

7. Germany pubmed.ncbi.nlm.nih.gov

Pharmacodynamic and pharmacokinetic study of a slow-release formulation of furosemide in man. [2013]

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

Furosemide compared with hydrochlorothiazide. Long-term treatment of hypertension. [2016]

9. England pubmed.ncbi.nlm.nih.gov

Long-term treatment with slow-release frusemide compared with thiazide treatment in arterial hypertension. [2017]