#1 Clinical Trials Search in Europe

Evaluating Citrulline, Folic Acid, Vericiguat, and Tadalafil Combination for Patients with Treatment-Resistant High Blood Pressure

2 1 1 1

What is this study about?

This clinical trial focuses on treatment-resistant hypertension, a condition where blood pressure remains high despite the use of multiple blood pressure medications. The study will test a combination of four substances: L-citrulline (an amino acid), folic acid (a B vitamin), vericiguat (a medication that stimulates an enzyme called soluble guanylate cyclase), and tadalafil (a medication that inhibits an enzyme called phosphodiesterase type 5) as add-on therapy for patients whose blood pressure is difficult to control with standard treatments.

The purpose of this trial is to evaluate how effective these substances are when used together to lower blood pressure in people with resistant hypertension. This is a three-way cross-over phase IIa trial, which means participants will receive different treatment combinations at different times during the study, allowing researchers to compare the effects of these combinations within the same individuals.

The study will measure changes in systolic blood pressure (the top number in a blood pressure reading) and diastolic blood pressure (the bottom number) using both office measurements and 24-hour ambulatory blood pressure monitoring (a method that measures blood pressure throughout the day and night). The trial will specifically look at patients who have high levels of certain substances in their blood that may contribute to their resistant hypertension.

1 Baseline Measurement & Treatment Assignment

Your blood pressure will be measured using a 24-hour ambulatory blood pressure monitor (ABPM) to establish your baseline blood pressure readings.

Your urine will be collected to measure albumin and creatinine levels, and a blood sample will be taken to count circulatory mature endothelial cells (CEC), which are cells that line your blood vessels.

You will then be assigned to one of three medication combinations, as this is a three-way crossover trial, meaning you will receive all three treatment combinations at different times.

2 First Treatment Period

You will take one of the following treatment combinations:

Option 1: Citrulline + Folic acid + Vericiguat + Tadalafil

Option 2: Citrulline + Folic acid + Vericiguat

Option 3: Citrulline + Folic acid + Tadalafil

The medications will include Vericiguat (Verquvo 2.5 mg film-coated tablets), Tadalafil (Tadalafil Krka 5 mg film-coated tablets), and Folic acid (Folsyra Evolan 5 mg tablets). Citrulline dosage is not specified in the provided information.

3 First Follow-up Assessment

After completing the first treatment period, your blood pressure will be measured again using the 24-hour ABPM.

Office blood pressure readings will also be taken to determine if you’ve reached the target systolic blood pressure (less than 140 mmHg).

Additional blood and urine samples will be collected to measure the same parameters as at baseline.

4 Second Treatment Period

You will switch to the second treatment combination that you haven’t received yet.

The dosage and frequency remain the same as in the first treatment period.

5 Second Follow-up Assessment

After completing the second treatment period, the same measurements will be taken again: 24-hour ABPM, office blood pressure readings, blood and urine samples.

6 Third Treatment Period

You will receive the final treatment combination that you haven’t tried yet.

The dosage and frequency remain consistent with previous treatment periods.

7 Final Assessment

After completing all three treatment periods, a final comprehensive assessment will be conducted with the same measurements as before.

The study team will compare how each treatment combination affected your blood pressure and other measured parameters.

The study is expected to run from May 2025 to February 2026, though individual participation duration is not specified.

Who Can Join the Study?

  • You must be between 18 and 80 years old at the time you give consent
  • You must be willing to provide written informed consent and agree to all study procedures
  • You must have high blood pressure measured in the office with a systolic pressure ≥ 140 mmHg and < 180 mmHg and/or a diastolic pressure ≥ 90 mmHg (systolic is the top number and diastolic is the bottom number in a blood pressure reading)
  • Your 24-hour blood pressure monitoring must show a systolic pressure > 130 mmHg and < 170 mmHg and/or diastolic pressure > 80 mmHg
  • You must have treatment-resistant hypertension, which means your blood pressure remains high despite taking at least 3 different blood pressure medications at optimal doses (including specific types of medications called ACE inhibitors or ARBs, calcium channel blockers, and diuretics)
  • Your high blood pressure must be confirmed by blood pressure monitoring and not be due to other causes (like not taking medications as prescribed)
  • You must have elevated NOX5/ADMA levels (greater than 170 pg/ml) in your blood (these are substances that affect blood vessel function)

Who Cannot Join the Study?

  • If you are pregnant or breastfeeding.
  • If you have liver problems or severe liver disease.
  • If you have severe kidney disease (estimated glomerular filtration rate less than 30 mL/min/1.73 m²).
  • If you have had a heart attack, stroke, or severe heart failure in the past 6 months.
  • If you are taking medications called nitrates (commonly prescribed for chest pain).
  • If you have a condition that causes very low blood pressure (systolic blood pressure below 90 mmHg).
  • If you have uncontrolled high blood pressure (systolic blood pressure above 180 mmHg).
  • If you are allergic to any of the study medications (citrulline, folic acid, tadalafil, or vericiguat).
  • If you have a rare eye disease called non-arteritic anterior ischemic optic neuropathy (NAION).
  • If you are currently participating in another clinical trial.
  • If you have any condition that the study doctor believes would make it unsafe for you to participate.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

No sites found in this category

Other Sites

Site Name City Country Status
Karolinska University Hospital Solna Sweden

Want to learn more about this study or check if you can participate? Contact us.

Trial status

Country Status Recruitment Start
Sweden Sweden
Recruiting
01.05.2025

Trial locations

Investigated drugs:

L-citrulline is an amino acid that helps blood vessels produce nitric oxide, which can widen blood vessels and improve blood flow. This may help lower blood pressure.

Folic acid is a B vitamin that plays a role in the production of nitric oxide in blood vessels. It’s being studied for its potential to improve blood vessel function and help lower blood pressure.

Vericiguat is a medication that works by enhancing the activity of an enzyme called soluble guanylate cyclase, which helps blood vessels relax and widen. This may help reduce blood pressure in patients with resistant hypertension.

Tadalafil is a medication that belongs to a class of drugs called phosphodiesterase type 5 (PDE5) inhibitors. It helps relax blood vessels and improve blood flow, which can lower blood pressure. It’s commonly used to treat erectile dysfunction but is being studied for its blood pressure-lowering effects in this trial.

Investigated diseases:

Treatment-resistant hypertension – A condition characterized by persistently high blood pressure that remains above target levels despite the concurrent use of three or more antihypertensive medications of different classes, one of which is usually a diuretic. In this form of hypertension, the blood vessels maintain high resistance to blood flow despite multiple medication therapies. This condition affects about 10% of all patients with hypertension and tends to be associated with older age, obesity, and certain comorbidities. The mechanisms involved may include excessive fluid retention, increased activation of the sympathetic nervous system, and alterations in hormones that regulate blood pressure. Over time, persistent elevated blood pressure can lead to changes in the structure and function of blood vessels and the heart.

Trial ID:
2024-520231-33-00
Trial Phase:
Therapeutic exploratory (Phase II)

Other Trials to Consider

  • Study of vicadrostat and empagliflozin combination in patients with type 2 diabetes, high blood pressure and cardiovascular disease

    Recruiting

    3 1 1
    Investigated diseases:
    Investigated drugs:
    Austria Belgium Bulgaria Croatia Czechia Denmark +17

  • A study to evaluate the effect of baxdrostat and dapagliflozin in reducing protein in the urine for patients with chronic kidney disease and high blood pressure

    Recruiting

    2 1 1
    Investigated drugs:
    Bulgaria Spain