Compensated Heart FailurePhase 4NCT01549158
Single Dose Study to Compare the Pharmacodynamics of Torasemide-PR 10 mg,Torasemide-IR 10 mg and Furosemide-IR 40 mg in Patients With Compensated Heart Failure
A Phase 4 study testing torasemide-PR, Furosemide-IR and torasemide-IR in people with Compensated Heart Failure, run by Ferrer Internacional S.A. at 1 site in Spain.
Trial summary
This is a randomized, open-label, blinded-endpoint, crossover, single dose study to compare the pharmacodynamics of Torasemide-PR 10 mg, Torasemide-IR10 mg and furosemide-IR 40 mg. 30 patients of both sexes with CHF with a maximum imbalance of 60:40% in either direction will be included in the study. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Compensated Heart Failure
- What is being tested?
- torasemide-PR, Furosemide-IR and torasemide-IR
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteSpain
- Study dates
- Feb 2012to Dec 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able to understand the nature of the study.
- Obtain signed informed consent form approved by the Ethics Committee of the hospital (CEIC).
- Male and female, ≥ 18 years at the time of the informed consent signature.
- Patients with compensated heart failure, grade II or III as defined by the European Society of Cardiology, with a duration of ≥ 3 months at the time of inclusion documented in the patient's record or patients who previously required diuretic therapy.
- Patients with stable heart failure on drug therapy. Stable drug therapy is defined as not having introduced any new drug for heart failure within 4 weeks prior to inclusion. Drugs doses could be adjusted during the study with the exception of the diuretics
- Lab analysis results, vital signs and ECG within normal ranges or not considered clinically significant by the investigator.
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- For women only, the patient must be:
- postmenopausal (≥ 1 year) or sterilized or,
- without risk of becoming pregnant, not lactating, have a negative pregnancy test at study entry and without intention of becoming pregnant during the study course and use effective contraception.
- Postmenopausal status is defined as 12 consecutive months of spontaneous amenorrhea or confirmed by the results of follicle stimulating hormone (FSH) > 40 mlU/mL or at least 6 months after oophorectomy (with or without hysterectomy) documented in the patients record.
- Body weight within the normal ranges (Quetelet's index between 19 and 30) expressed as weight (kg) /height (m2).
Who cannot join
- Hospitalization due to heart failure, acute coronary syndrome, myocardial infarction, cardiac catheterization, revascularization, cardiac arrhythmia, transient ischemic attack or stroke, cardiac arrhythmia within 6 weeks prior to inclusion or major surgery including cardiac thoracic or within 8 weeks prior to inclusion.
- Symptoms of angina at rest or with minimal activity (class III or IV, Canadian Cardiovascular Society).
- Severe aortic or mitral stenosis or clinically significant valvular heart disease that can lead to surgery within 12 months after inclusion.
- Hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive pericarditis or clinically significant congenital heart disease.
- If ventricular assist devices, continuous inotropic therapy or hospitalization is considered necessary in case of refractory end-stage heart failure.
- Implementation of CRT within 3 months or cardioverter defibrillator in the 4 weeks before inclusion.
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- High probability of receiving a heart transplant within 6 months after inclusion.
- Main organ transplant (ex. lungs, liver, kidney, heart, bone).
- Positive surface antigen of hepatitis B, hepatitis C or HIV or a known diagnosis of AIDS.
- Medical history or evidence of drug or alcohol abuse in the 3 months prior to inclusion.
- Concomitant cardiovascular disease that is expected to reduce life expectancy to less than one year.
- Scheduled routine iv infusions for heart failure (ex. inotropes, vasodilators, diuretics) or routine ultrafiltration.
- Digoxin therapy at steady state (approximately 6 hours post-dose) exceeding 1.0 ng/mL at inclusion.
- Chronic therapy with antiarrhythmic, antiepileptic drugs, eplerenone and espironolactone except amiodarone and beta-blockers.
- Current intake or within 14 days prior to inclusion of a potent inhibitor of CYP2C9
- Current intake or within 28 days prior to inclusion of a potent inducer of CYP2C9.
- Participation, in the 60 days or 5 half lives preceding the inclusion in the study, in other clinical trial.
- Systolic blood pressure > 150mm Hg diastolic blood pressure > 95 mmHg, confirmed on 2 separate visits before inclusion.
- Heart rate in supine > 100 beats/min after 5 minute rest or untreated symptomatic bradycardia within one month prior to inclusion.
- Total bilirubin > 1.5 times ULN, or ALT or AST > 3 times ULN.
- Estimated GFR > 30 ml/min/1.73 m2 calculated by the modification of diet in renal disease (RD).
- Chronic treatment with NSAIDs (> 7 days), except aspirin < 325 mg dose.
- Uncontrolled insulin-dependent diabetes.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Centre d'Investigació de Medicaments (CIM), Hospital de la Santa Creu i Sant Pau
Barcelona, 08025
About this study
Official title: Randomized, Open-Label, Blinded-Endpoint, Crossover, Single Dose Study to Compare the Pharmacodynamics of Torasemide-PR 10 mg,Torasemide-IR 10 mg and Furosemide-IR 40 mg, in Patients With Compensated Heart Failure (CHF).
This is a randomized, open-label, blinded-endpoint, crossover, single dose study to compare the pharmacodynamics of Torasemide-PR 10 mg, Torasemide-IR10 mg and furosemide-IR 40 mg. 30 patients of both sexes with CHF with a maximum imbalance of 60:40% in either direction will be included in the study. Patients with compensated heart failure, grade II or III as defined by the European Society of Cardiology, with a duration of ≥ 3 months at the time of inclusion documented in the patient's record or patients who previously required diuretic therapy.
Principal variable will be the efficiency of sodium excretion that will be assessed as the ratio between the average drug-induced natriuresis and the average drug recovered in urine over 24 hours.
The difference between the efficiency of 24 hour sodium excretion following administration of torasemide PR and furosemide will be formally tested by means of a Students t-test for paired samples. The test will be two-sided at 5% significance level. Efficiency changes over time will also be assessed, however will not be subject to formal statistical testing.
- Conditions
- Compensated Heart Failure
- Being tested
- torasemide-PR, Furosemide-IR, torasemide-IR
- Keywords
- loop diuretics, torasemide prolonged release, torasemide immediate release, Sutril Neo, pharmacodynamic profile of Torasemide-PR
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
torasemide-PRDrug
Single oral dose of torasemide PR 10 mg
Furosemide-IRDrug
Single oral dose of furosemide IR 40 mg
torasemide-IRDrug
Single oral dose of torasemide IR 10 mg
| Study group | Role | What they receive |
|---|---|---|
| Torasemide PR 10 mg | Experimental | Not described Receives: Drug: torasemide-PR |
| Furosemide-IR 40 mg | Active comparator | Not described Receives: Drug: Furosemide-IR |
| Torasemide-IR 10 mg | Active comparator | Not described Receives: Drug: torasemide-IR |
What is being measured
The primary outcome is the main question the study is designed to answer.
The efficiency of sodium excretion
Will be assessed as the ratio between the average drug-induced natriuresis and the average drug recovered in urine over 24 hours.
Measured: 24 hours
Secondary outcomes (1)
Pharmacokinetic plasma parameters and pharmacokinetic urine parameters
Pharmacokinetic plasma parameters (Cmax, AUC0-t, AUC0-∞, t ½, Vd / F, Cl / F), pharmacokinetic urine parameters (ERFco , Ae24h, Ae ∞) and urine pharmacodynamic variables will be presented descriptively with no formal statistical testing.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2012 (estimated)
- Study startFeb 2012
- Primary completionOct 2012
- Study completionDec 2012
Why it stopped: Slow recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Compensated Heart FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ferrer Internacional S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01549158
- Sponsor's protocol ID
- P-110875-01
- Status last verified
- Apr 2013
- First submitted
- 6 Mar 2012
- Last updated
- 25 Apr 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Ballester MR, Roig E, Gich I, Puntes M, Delgadillo J, Santos B, Antonijoan RM. Randomized, open-label, blinded-endpoint, crossover, single-dose study to compare the pharmacodynamics of torasemide-PR 10 mg, torasemide-IR 10 mg, and furosemide-IR 40 mg, in patients with chronic heart failure. Drug Des Devel Ther. 2015 Aug 5;9:4291-302. doi: 10.2147/DDDT.S86300. eCollection 2015.
PubMed 26273191
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Open-Label, Blinded-Endpoint, Crossover, Single Dose Study to Compare the Pharmacodynamics of Torasemide-PR 10 mg,Torasemide-IR 10 mg and Furosemide-IR 40 mg, in Patients With Compensated Heart Failure (CHF).
- ClinicalTrials.gov ID
- NCT01549158
- Acronym / sponsor ID
- P-110875-01
- Conditions
- Compensated Heart Failure
- Keywords
- loop diuretics, torasemide prolonged release, torasemide immediate release, Sutril Neo, pharmacodynamic profile of Torasemide-PR
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Ferrer Internacional S.A.Industry (pharma, biotech, devices)
- Study start
- Feb 2012
- Primary completion
- Oct 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 9 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, open-label, blinded-endpoint, crossover, single dose study to compare the pharmacodynamics of Torasemide-PR 10 mg, Torasemide-IR10 mg and furosemide-IR 40 mg. 30 patients of both sexes with CHF with a maximum imbalance of 60:40% in either direction will be included in the study. Patients with compensated heart failure, grade II or III as defined by the European Society of Cardiology, with a duration of ≥ 3 months at the time of inclusion documented in the patient's record or patients who previously required diuretic therapy.
Principal variable will be the efficiency of sodium excretion that will be assessed as the ratio between the average drug-induced natriuresis and the average drug recovered in urine over 24 hours.
The difference between the efficiency of 24 hour sodium excretion following administration of torasemide PR and furosemide will be formally tested by means of a Students t-test for paired samples. The test will be two-sided at 5% significance level. Efficiency changes over time will also be assessed, however will not be subject to formal statistical testing.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Torasemide PR 10 mg | Experimental | Drug: torasemide-PR |
| Furosemide-IR 40 mg | Active comparator | Drug: Furosemide-IR |
| Torasemide-IR 10 mg | Active comparator | Drug: torasemide-IR |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Able to understand the nature of the study.
- Obtain signed informed consent form approved by the Ethics Committee of the hospital (CEIC).
- Male and female, ≥ 18 years at the time of the informed consent signature.
- Patients with compensated heart failure, grade II or III as defined by the European Society of Cardiology, with a duration of ≥ 3 months at the time of inclusion documented in the patient's record or patients who previously required diuretic therapy.
- Patients with stable heart failure on drug therapy. Stable drug therapy is defined as not having introduced any new drug for heart failure within 4 weeks prior to inclusion. Drugs doses could be adjusted during the study with the exception of the diuretics
Key exclusion criteria (23 listed)
- Hospitalization due to heart failure, acute coronary syndrome, myocardial infarction, cardiac catheterization, revascularization, cardiac arrhythmia, transient ischemic attack or stroke, cardiac arrhythmia within 6 weeks prior to inclusion or major surgery including cardiac thoracic or within 8 weeks prior to inclusion.
- Symptoms of angina at rest or with minimal activity (class III or IV, Canadian Cardiovascular Society).
- Severe aortic or mitral stenosis or clinically significant valvular heart disease that can lead to surgery within 12 months after inclusion.
- Hypertrophic obstructive cardiomyopathy, active myocarditis, constrictive pericarditis or clinically significant congenital heart disease.
- If ventricular assist devices, continuous inotropic therapy or hospitalization is considered necessary in case of refractory end-stage heart failure.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| torasemide-PRSingle oral dose of torasemide PR 10 mg | Drug | Torasemide PR 10 mg |
| Furosemide-IRSingle oral dose of furosemide IR 40 mg | Drug | Furosemide-IR 40 mg |
| torasemide-IRSingle oral dose of torasemide IR 10 mg | Drug | Torasemide-IR 10 mg |
Primary outcome
The efficiency of sodium excretion
Time frame: 24 hours
Will be assessed as the ratio between the average drug-induced natriuresis and the average drug recovered in urine over 24 hours.
1 secondary outcome
Pharmacokinetic plasma parameters and pharmacokinetic urine parameters
Time frame: 24 hours
Results and safety
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2013.
- Derived from this study: PubMed 26273191Ballester MR, Roig E, Gich I, Puntes M, Delgadillo J, Santos B, Antonijoan RM. Randomized, open-label, blinded-endpoint, crossover, single-dose study to compare the pharmacodynamics of torasemide-PR 10 mg, torasemide-IR 10 mg, and furosemide-IR 40 mg, in patients with chronic heart failure. Drug Des Devel Ther. 2015 Aug 5;9:4291-302. doi: 10.2147/DDDT.S86300. eCollection 2015.
Related trials for Compensated Heart Failure
RecruitingObservational study
Circulating Markers That Underlie the Transition From Compensated Hypertrophy to Heart Failure
Acute Decompensated Heart Failure, Heart Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing torasemide-PR, Furosemide-IR and torasemide-IR in people with Compensated Heart Failure, run by Ferrer Internacional S.A. at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The efficiency of sodium excretion (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01549158, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2013.