Table 2.

Eligibility criteria

Inclusion criteria

Hypertensive patients aged ≥18 years of age

Patients will all have hypertension that is not controlled to home target: SBP >135 mm Hg and/or DBP >85 mm Hg on therapy with 1 or more antihypertensive drugs for at least 3 months

Able to attend one of the 3 study centers

Exclusion criteria

Inability to give informed consent

Participation in a clinical study involving an investigational drug or device within 3 months of screening

Secondary or accelerated hypertension

Diabetes mellitus (type 1 or type 2)

eGFR <60 ml/minute, hyponatremia, hypokalemia

Pregnancy, breast feeding

Women of childbearing potential who are unwilling to use effective contraception

Childbearing potential is defined as women who have experienced menarche and who have not undergone successful surgical sterilization or who are not postmenopausal (irregular menstrual periods, or amenorrhea >12 months, with serum follicle-stimulating hormone (FSH) >35 mIU/ml; women taking hormone replacement therapy (HRT)

Women of childbearing potential will be eligible if they are willing to use acceptable contraception (combined oral contraceptives, progesterone only contraceptives, intrauterine device, barrier methods) or they are abstinence due to lifestyle choice or their partner is sterile (vasectomy)

Anticipated change of medical status during the trial (e.g., surgical intervention requiring >2 weeks convalescence)

Recent (<6 months) cardiovascular event requiring hospitalization (e.g., myocardial infarction or stroke)

Requirement for study drug or other loop-diuretic for reason other than to treat hypertension

Clinically relevant contraindication to treatment with torasemide: hypersensitivity, hereditary problems of glucose intolerance, Lapp lactase deficiency of glucose–galactose malabsorption

Current therapy for cancer

Concurrent chronic illness, or other reasons likely to preclude 18-week participation in the study

Any concomitant condition that, in the opinion of the investigator, may adversely affect the safety and/or efficacy of the study drug or severely limit that patients life-span or ability to complete the study (e.g., alcohol or drug abuse, disabling or terminal illness, severe liver impairment, mental disorders)

Treatment with any of the following medications

Oral corticosteroids within 3 months of screening. Treatment with systemic corticosteroids is also prohibited during study participation

Chronic stable use, or unstable use of NSAIDs (other than low dose aspirin or occasional over the counter analgesic doses) is prohibited. Chronic use is defined as >3 consecutive days of treatment per week. In addition, intermittent use of NSAIDs is discouraged throughout the study. For those requiring analgesics during the study, paracetamol or opiate drugs are recommended

Use of lithium

Participants on the following medications may be included provided they meet the following criteria

Use of thiazide or loop-diuretics prior to the study if the diuretic can be stopped for 2 weeks (washout) before the study medication administered

The use of short acting nitrates (e.g., sublingual nitroglycerin) is permitted. However, participants should avoid short acting oral nitrates within 4 hours of screening or a subsequent visit

The use of long acting nitrates (e.g., Isordil) is permitted but the dose must be stable for at least 2 weeks prior to screening

The use of sympathomimetic decongestants is permitted, though not within 24 hours of any study visit/BP assessment

The use of theophylline is permitted but the dose must be stable for at least 4 weeks prior to screening and throughout the study

The use of phosphodiesterase type V inhibitors is permitted. However, study participants must refrain from taking these medications for at least 7 days prior to screening or any subsequent study visit

Abbreviations: BP, blood pressure; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; NSAIDs, non-steroidal anti- inflammatory drugs; SBP, systolic blood pressure.