Participants are randomly assigned to receive either a daily oral pill such as edoxaban or apixaban, an injectable medicine such as dalteparin, tinzaparin, enoxaparin, or rivaroxaban, or a placebo that looks the same but contains no active drug. Over several months, they will have regular check‑ups that may include simple scans of the lungs to confirm whether the clot has changed, and they will complete questionnaires about their daily well‑being. The study does not require any special procedures beyond the usual care for cancer and clot management.

In the trial, participants are randomly assigned to either keep taking the medication right up to the morning of the surgery or to stop it three days before the procedure. The operation is performed using cardiopulmonary bypass, a technique that temporarily takes over the work of the heart and lungs. After surgery, patients are monitored for about a month to see whether they develop problems such as damage to the heart muscle measured by an increase in high-sensitivity troponin I, a blood test that shows heart injury, or experience low cardiac output syndrome, which means the heart is not pumping enough blood. Other complications that are checked include a rare condition called euglycaemic ketoacidosis (a buildup of acids despite normal blood sugar), acute renal failure (sudden kidney problems) assessed using the KDIGO scoring system, need for additional hospital stays for heart failure, and overall survival. The follow‑up period lasts 30 days after the surgery, during which length of hospital stay and quality of life are also recorded.

Table of Contents

• What is Torasemide?
• How Torasemide Works
• Medical Conditions Treated with Torasemide
• Different Formulations of Torasemide
• Torasemide vs. Furosemide
• Dosage Information
• Potential Side Effects
• Use in Special Populations
• Ongoing Research and Future Directions

What is Torasemide?

Torasemide (also spelled as torsemide) is a medication that belongs to a class of drugs called loop diuretics. It is prescribed to remove excess fluid from the body in conditions where fluid retention is a problem. Torasemide is sold under various brand names including Demadex, Tortas, and Wator ^[1].

As a loop diuretic, torasemide works by preventing your kidneys from absorbing too much salt, which allows the salt to instead be passed in your urine. When salt is filtered from your blood by the kidneys, water is also drawn out, which helps reduce fluid buildup in your body ^[2].

How Torasemide Works

Torasemide acts on a specific part of the kidney called the ascending loop of Henle. It inhibits what’s known as the Na+/K+/2Cl- transport system and blocks chloride channels. This prevents sodium and chlorine ions from being reabsorbed into your bloodstream, which significantly increases urine volume ^[3].

By increasing urine production, torasemide helps reduce fluid retention (edema) in the body. This can relieve symptoms like swelling in the legs and ankles, shortness of breath, and can reduce strain on the heart in patients with heart failure ^[4].

Unlike some other diuretics, torasemide has a longer elimination half-life, which means it stays active in your body for longer periods, potentially allowing for once-daily dosing instead of multiple doses throughout the day ^[5].

Medical Conditions Treated with Torasemide

Torasemide is prescribed for several medical conditions that involve fluid retention:

Heart Failure

In heart failure, the heart cannot pump blood effectively, leading to fluid buildup in the body. Torasemide helps reduce this fluid accumulation, decreasing the workload on the heart and improving symptoms like shortness of breath and swelling ^[6]. Studies have shown that torasemide may have additional benefits for heart failure patients beyond its diuretic effects, including potential effects on myocardial remodeling and fibrosis (scarring) ^[7].

Hypertension (High Blood Pressure)

Torasemide can be used alone or in combination with other medications to treat high blood pressure. By reducing fluid volume in the blood vessels, it helps lower blood pressure ^[8]. Research suggests that torasemide may be effective in patients with various genetic predispositions to hypertension, including those related to lanosterol and uromodulin genes ^[1].

Edema (Fluid Retention)

Torasemide is effective in treating edema associated with various conditions:

• Liver disease (hepatic edema)
• Kidney disease (renal edema)
• Fluid in the lungs (pulmonary congestion)
• Right heart failure with tricuspid regurgitation ^[9]

Postpartum Hypertension

Research is investigating the use of torasemide for the prevention of persistent hypertension after childbirth in women who had preeclampsia during pregnancy ^[10].

Different Formulations of Torasemide

Torasemide is available in different formulations, each with its own characteristics:

Immediate Release (IR) Torasemide

This is the standard formulation that releases the medication quickly after taking it. It provides a rapid diuretic effect but may have a shorter duration of action ^[11]. The immediate release formulation can sometimes cause large and abrupt urination that might lead to incontinence in some patients ^[12].

Extended Release (ER) or Prolonged Release (PR) Torasemide

This formulation is designed to release the medication more slowly over time, providing a more gradual and prolonged effect. Studies suggest that extended-release torasemide may offer several advantages:

• More gradual urination, which may be more comfortable and reduce the risk of incontinence ^[12]
• Prolonged duration of action, which may improve sodium excretion even when patients consume a high-salt diet ^[12]
• Potentially improved effects on reducing symptoms in patients with heart failure and overactive bladder ^[13]

Recent research is investigating whether extended-release torasemide may enhance sodium excretion after meals (particularly after lunch) compared to immediate-release torasemide, which could provide better fluid control throughout the day ^[14].

Fixed-Dose Combinations

Research is also exploring the use of torasemide in fixed-dose combinations with other medications, such as spironolactone (a potassium-sparing diuretic) ^[15]. These combinations may provide complementary effects in managing conditions like heart failure and hypertension.

Torasemide vs. Furosemide

Furosemide (brand name Lasix) is another common loop diuretic that has been used for many years. Several studies have compared torasemide to furosemide:

Similarities

• Both are loop diuretics that work through similar mechanisms
• Both effectively reduce fluid retention and edema
• Both can be used to treat heart failure, hypertension, and edema ^[16]

Differences and Potential Advantages of Torasemide

• Longer half-life: Torasemide has a longer elimination time, which may allow for once-daily dosing compared to multiple daily doses of furosemide ^[5]
• Better bioavailability: Torasemide is more consistently absorbed when taken orally (around 80-90% compared to furosemide’s more variable 10-100%) ^[17]
• Less electrolyte disturbance: Some studies suggest torasemide may cause fewer electrolyte imbalances than furosemide ^[5]
• Additional effects: Research indicates torasemide may have additional benefits beyond its diuretic effects, including potential anti-fibrotic effects in the heart, which could be beneficial for heart failure patients ^[7]

The ongoing TRANSFORM-HF clinical trial is directly comparing torasemide versus furosemide for management of heart failure to determine if one medication offers superior clinical outcomes over the other ^[18].

Conversion Between Medications

When switching between these medications, the general dosing equivalence is:

• 1 mg torasemide ≈ 2-4 mg furosemide ^[19]

For example, if you were taking furosemide 40 mg, you might be switched to torasemide 10-20 mg, though the exact dosing should be determined by your healthcare provider.

Dosage Information

Torasemide dosing depends on the condition being treated and the individual patient. Always follow your healthcare provider’s instructions. General dosing guidelines include:

Heart Failure

• Starting dose: Usually 10-20 mg once daily
• Dose may be increased approximately twofold if adequate effect is not achieved ^[20]

Hypertension

• Starting dose: 5-10 mg once daily
• Can be increased up to 20 mg daily if needed, in some cases up to 40 mg ^[20]

Extended Release Formulations

Dosing for extended-release formulations may differ slightly. For example:

• 24 mg of extended-release torasemide is often equivalent to 20 mg of immediate-release torasemide ^[14]

Special Dosing Considerations

Patients with kidney impairment may need adjusted doses based on their level of kidney function. Your healthcare provider will determine the appropriate dose based on your specific situation ^[21].

Potential Side Effects

Like all medications, torasemide can cause side effects. Not everyone will experience these, and many side effects are manageable with proper monitoring.

Common Side Effects

• Increased urination: This is an expected effect of the medication
• Dizziness or lightheadedness: Especially when standing up quickly, due to lowered blood pressure
• Headache
• Fatigue or weakness

Electrolyte Imbalances

Torasemide can affect the levels of important minerals in your body, including:

• Low potassium (hypokalemia): May cause muscle weakness, cramps, or irregular heartbeat ^[10]
• Low sodium (hyponatremia): May cause confusion, headache, or seizures in severe cases
• Low magnesium or calcium: May affect nerve and muscle function

Your doctor will likely monitor your electrolyte levels with blood tests and may recommend supplements or dietary changes if needed.

Less Common but Serious Side Effects

• Acute kidney injury: Particularly in patients with pre-existing kidney problems ^[10]
• Hearing problems: Rarely, reversible hearing loss or ringing in the ears (tinnitus) may occur, especially with high doses ^[10]
• Allergic reactions: Such as rash, itching, or in severe cases, difficulty breathing
• Gout: Torasemide can increase uric acid levels, potentially triggering gout attacks in susceptible individuals

Effects on Breast Milk

For breastfeeding mothers, research is investigating whether torasemide passes into breast milk and its potential effects ^[10]. Discuss the risks and benefits with your healthcare provider if you are breastfeeding.

Use in Special Populations

Patients with Kidney Impairment

Torasemide can be used in patients with kidney impairment, but dosing may need to be adjusted. Studies show that torasemide can still be effective in patients with moderate to severe renal insufficiency, though careful monitoring is needed ^[21].

Patients with Heart Failure and Kidney Impairment

Many patients have both heart failure and kidney problems. Research is investigating optimal diuretic strategies for these patients, including the use of torasemide ^[21].

Pregnant and Postpartum Women

Studies are examining the use of torasemide for preventing persistent hypertension after childbirth in women who had preeclampsia during pregnancy ^[10]. Always consult with your healthcare provider about medication use during pregnancy or while breastfeeding.

Patients with Overactive Bladder and Heart Failure

Some patients with heart failure also experience symptoms of overactive bladder (frequent urination, urgency, or urgency incontinence). Extended-release torasemide may help manage both conditions by providing a more gradual diuretic effect ^[13].

Ongoing Research and Future Directions

Several clinical trials are currently investigating various aspects of torasemide treatment:

TRANSFORM-HF Trial

This large study is directly comparing torasemide versus furosemide for management of heart failure to determine if one medication offers superior clinical outcomes in terms of mortality, hospitalizations, and quality of life ^[18].

Extended Release Formulations

Multiple studies are examining whether extended-release torasemide offers advantages over immediate-release formulations, particularly for:

• Maintaining natriuretic effects throughout the day, especially after meals ^[14]
• Reducing symptoms of overactive bladder in heart failure patients ^[13]
• Improving patient comfort and compliance ^[12]

Personalized Medicine Approaches

Research is investigating whether genetic factors may predict response to torasemide. For example, studies are looking at how variations in genes like uromodulin (UMOD) and lanosterol synthase (LSS) might affect response to torasemide in hypertension treatment ^[1].

Fixed-Dose Combinations

Development of fixed-dose combinations of torasemide with other medications, such as spironolactone, may provide more convenient and potentially more effective treatment options for heart failure and hypertension ^[15].

Weight-Based Dosing Strategies

Some researchers are studying whether individualizing torasemide dosing based on a patient’s weight and symptoms might improve outcomes compared to standard fixed-dose regimens ^[22].

These ongoing research efforts aim to optimize the use of torasemide for various conditions and potentially expand its therapeutic applications.

Table of Contents

• What THEOPHYLLINE ANHYDROUS is in these trials
• Clinical trial in post-dural puncture headache (PDPH)
• What outcomes were measured in the PDPH trial
• Side effects monitored in the PDPH trial
• Clinical study in chronic total coronary occlusion (CTO) imaging
• Key imaging definitions and endpoints in the CTO study

What THEOPHYLLINE ANHYDROUS is in these trials

In the provided clinical trial records, the drug appears as an oral tablet used to treat headache after a dural puncture and as an intravenous solution for injection used in a cardiovascular imaging study.^[1][2]

One listed “other name” (synonym/brand name) for the oral tablet is Quibron-T/SR tablets.^[1]

The cardiovascular study lists synonyms for the active substance such as ANHYDROUS THEOPHYLLINE and “THEOPHYLLINE (ANHYDROUS).”^[2]

Clinical trial in post-dural puncture headache (PDPH)

This study asked whether oral theophylline is more effective than oral sumatriptan for treating PDPH.^[1]

The trial describes PDPH as a frequent complication after procedures involving dural puncture for spinal anesthesia or after accidental dural puncture during epidural anesthesia.^[1]

It was a prospective, randomized, double-blind, phase four clinical trial that included 60 patients with PDPH, split into two equal groups of 30 patients each.^[1]

The theophylline group received an oral theophylline tablet at 150 mg every 12 hours.^[1]

The comparator group received oral sumatriptan succinate at 25 mg every 12 hours.^[1]

What outcomes were measured in the PDPH trial

The main outcome was pain severity measured with the Numeric Pain Rating Scale (NPRS), which is an 11-point scale from 0 to 10 where 0 means no pain and 10 means the worst possible pain.^[1]

Pain scores were collected before treatment and then at 2, 6, 12, 18, and 24 hours, then every 12 hours until 48 hours after starting treatment.^[1]

The trial planned to report NPRS results as both median (range) and mean ± standard deviation over the 48-hour timeframe.^[1]

A secondary outcome was the duration of PDPH (in hours), defined as the time from headache onset until the NPRS score became 3 or less.^[1]

Another secondary outcome was the length of hospital stay (in days), measured from hospital admission until discharge, over the same 48-hour evaluation period.^[1]

Side effects monitored in the PDPH trial

The study tracked the number and rate of treatment-related side effects within 48 hours after starting treatment.^[1]

Side effects listed for monitoring included palpitations (feeling of fast or irregular heartbeat), dizziness, gastric irritation (stomach irritation), nausea/vomiting, diarrhea, warm sensations in the body, tingling sensation, and tightness in the chest, throat, neck, or jaws.^[1]

Clinical study in chronic total coronary occlusion (CTO) imaging

Another provided record describes a study in patients with chronic total occlusion of a coronary artery (a long-lasting complete blockage of a heart artery).^[2]

The main objective was to evaluate how well coronary CT angiography with myocardial perfusion imaging at stress and rest matches (concordance) stress cardiac MRI for detecting ischemia and viability in CTO patients.^[2]

In this study record, the drug listed is an IV product containing the active substance THEOPHYLLINE ANHYDROUS (route: intravenous), with a listed maximum daily dose amount of 200 mg and a maximum treatment period of 4 (time unit code provided in the record).^[2]

The product name shown is “Eufilina Venosa 200 mg solution for injection.”^[2]

Key imaging definitions and endpoints in the CTO study

The study’s primary endpoints include measures of viability, myocardial ischemia, and how CTO is defined and classified.^[2]

For viability, one imaging criterion was “late enhancement” in more than 50% of the thickness of the affected myocardial wall using the 17-segment model, reported as the number of segments meeting the criterion.^[2]

Another viability criterion looked at mean myocardial thickness less than 5 mm or 3 mm in segments with movement (motility) impairment, also counted by number of segments meeting the criterion.^[2]

For myocardial ischemia, the study defined it as an inducible and persistent perfusion defect during stress that significantly improves or resolves at rest and exceeds the extent of myocardial scar in the same segment on late enhancement images, again reported as the number of segments showing ischemia.^[2]

The CTO definition was absence of antegrade coronary flow through the coronary stenosis, allowing that there may be collateral flow as long as there is no flow through the lesion.^[2]

The study planned to classify CTO as definite if there is evidence the occlusion lasted more than three months, and probable if duration evidence is not available.^[2]

Secondary endpoints and methods included baseline cardiac MRI and follow-up at 6 months, CT imaging as part of routine pre-procedural evaluation, adverse event definitions using CTO-ARC, and arrhythmogenic substrate evaluation using late enhancement images and specified software.^[2]