Heart FailurePhase 4NCT00806910
Diuretic and Renal Effects of Vaprisol When Administered Along With Furosemide and Nesiritide Continuous Infusion
A Phase 4 study testing Conivaptan in people with Heart Failure, run by Albert Einstein Healthcare Network.
Trial summary
Heart Failure is a growing and challenging public health concern in the United States. Heart failure commonly manifests as a syndrome of salt and water retention. Arginine vasopressin is a peptide hormone that is intimately involved in salt and water homeostasis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- Conivaptan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Oct 2008to Feb 2010
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients over the age of 18 and able to consent
- LVEF ≤40% (as measured within last 6 months before entering into the study)
- Patients with Acute Decompensated Heart Failure (ADHF) (NYHA class 3 \& 4)
- Patients with estimated GFR >40ml/min as calculated by Cockcroft-Gault or MDRD formula
- Serum Sodium level <135 meq/L
- Ability to understand and willing to sign informed consent
- Willingness to follow-up in the clinic as outpatient
Who cannot join
- Patients with Acute Coronary Syndrome (ACS: Unstable angina, NSTEMI or STEMI)
- Patients on pressors (including Vasopressin analogs) for hemodynamic stability
- Supine systolic blood pressure <100 mm Hg
- Hypersensitivity to Conivaptan
- Concomitant use of medications that affects hepatic drug metabolism (e.g. Ketoconazole, Itraconazole, Ritonavir, Indinavir, Clarithromycin etc.)
- Significant liver dysfunction (ALT \& AST more than twice the upper limit of normal)
Show all 27Show fewer
- Uncontrolled bradyarrhythmias or tachyarrhythmias
- Pacemaker or defibrillator implantation or other cardiac surgery <60 days
- Severe obstructive pulmonary disease
- Significant uncorrected valvular or congenital heart disease
- Obstructive cardiomyopathy
- Significant renal impairment (defined as a serum creatinine >2.5 mg/dL or creatinine clearance <40 ml/min).
- Radiocontrast infusion within <7 days
- Pregnant or lactating female subject
- Untreated severe hyperthyroidism, hypothyroidism or adrenal insufficiency
- Expected requirement for emergent treatment of hypernatremia during the course of the study
- Known urinary outflow obstruction, unless subject is, or can be catheterized during the study
- Serum albumin < 1.5 gm/dl documented any time during any time during seven days prior to study drug administration
- Any concurrent illness, which in opinion of the investigator, may interfere with treatment or evaluation of safety.
- White blood cell count (WBC) count < 3000 /mL documented any time during seven days prior to study drug administration or anticipated drop in WBC count <3000/mL during the period of study due to chemotherapy.
- Participation in another clinical trial of an investigational drug (including placebo) or device within 30 days of screening for entry into the present study
- Subject has moderate ascites on physical examination secondary to hepatic dysfunction (ascites primarily related to cardiac dysfunction will be allowed as long as subject does not have cardiac cirrhosis).
- Subject has moderate to severe hepatic impairment as evidenced by Child-Pugh B or C criteria.
- Subject has a history of hepatic encephalopathy, hematemesis or melena.
- Subjects with altered mental status due to severe hyponatremia.
- Patient belonging to a vulnerable population such as institutionalized person, prisoners and persons with decisional incapacity or dementia.
- Patients on medications which are known to cause drug interactions such as Nicardipine, lovastatin, Ritonovir, Doxorubicin Etc
About this study
Official title: Evaluation of the Diuretic and Renal Effects of Vaprisol When Administered Along With Furosemide and Nesiritide Continuous Infusion
Heart Failure is a growing and challenging public health concern in the United States. Heart failure commonly manifests as a syndrome of salt and water retention. Arginine vasopressin is a peptide hormone that is intimately involved in salt and water homeostasis. AVP is released into the circulation in response low blood volume and hypernatraemia. Despite fluid overload, vasopressin levels are often inappropriately elevated in patients with heart failure and LV dysfunction. Data suggest that vasopressin may also contribute to the deleterious circulatory response in patients with heart failure and play a role in the development and progression of the disease process. In their study, Udelson et al. showed that vasopressin receptor antagonism with Conivaptan resulted in significant diuresis with stable hemodynamics in advanced heart failure patients. Currently Intravenous diuretics and vasodilators are the standard of care in treating patients with acute decompensated heart failure. We will be studying the renal and diuretic effects of add on therapy with intravenous Conivaptan in patients receiving intravenous Nesiritide and intravenous diuretics.
Read the detailed description
Heart failure effects 5 to 6 million Americans and is increasing in prevalence. There are about 550, 000 new cases of heart failure every year and about 3 million admissions for acute decompensated heart failure every year. The total cost of heat failure on the health systems is upwards of 35 billion dollars per year. Despite advances in medical care, the hospital readmission rate is 20% at one month and 50% at six months. This prevailing situation mandates further exploration of novel therapeutic targets to treat this complex disease.
Vasopressin levels are often elevated in patients with heart failure and LV dysfunction which is paradoxical and inappropriate. It has been hypothesized that high levels of circulating vasopressin may play an important role not only in the pathophysiology of the heart failure syndrome but also contribute to its disease progression.
Studies have shown that Conivaptan, a Vasopressin antagonist results in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. No consensus has been reached for Conivaptan to be used as a sole agent in Acute Decompensated Heart Failure (ADHF) patients and IV loop diuretics and/or vasodilators such as Nesiritide are used as the prime treatment for vascular congestion. This prevailing situation brings the questions whether, Conivaptan can be used as an adjunct to IV Furosemide and/or Nesiritide presenting with ADHF.We intend to investigate this question in a cohort of heart failure patients with hyponatremia.
This study will enroll 60 patients ( who meets all the inclusion criteria and none of the exclusion criteria), admitted to the Albert Einstein Medical Center with the diagnosis of Acute Decompensated Heart Failure (New York Heart Association class 3 and 4). The study population will be divided into 2 groups; a treatment group and a placebo group as described below. Each group will be comprised of 30 patients.
The treatment group will be treated with Nesiritide infusion, intravenous Furosemide (either continuous infusion or bolus injection- total dose of Furosemide received at the end of the study will be calculated) and IV Vaprisol. The placebo group will be given Nesiritide infusion and intravenous Furosemide(either continuous infusion or bolus injection) and placebo. Treatment will be continued in both groups for 24-36 hours.
- Conditions
- Heart Failure
- Being tested
- Conivaptan, Placebo
- Keywords
- Heart Failure, conivaptan, Diuresis
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ConivaptanDrug
Also called Vaprisol
IV Vaprisol initially at 20 mg IV injection over 30 minutes, followed by a 20 mg IV infusion over the next 24 hours (i.e. 20 mg bolus, 20 mg continuous infusion approximately 24 hrs).
PlaceboOther
Also called Saline
Placebo (will be given at the same rate of Vaprisol given in the treatment arm)
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Active comparator | Subjects will be treated with Intravenous Vaprisol along with Nesiritide infusion and intravenous Furosemide (either continuous infusion or bolus injections - total dose of Furosemide received will be calculated at the end of the study). Receives: Drug: Conivaptan |
| Placebo | Placebo comparator | Subjects will be given Placebo (at the same rate of Vaprisol given in the treatment arm) along with Nesiritide infusion and intravenous Furosemide (either continuous infusion or bolus injections - total dose of Furosemide received will be calculated at the end of the study). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Degree of diuresis as measured by weight change and intake and output measurement
Measured: Post infusion, Pre discharge and at 30 day Post discharge
Secondary outcomes (7)
Length of stay (LOS) in hospital
Measured: Concurrent
Clinical status based on NYHA criteria
Measured: Pre-discharge and 30-day post-discharge follow up
Serum electrolytes
Measured: Pre and Post infusion
BUN and Serum Creatinine concentration
Measured: Post infusion, Pre discharge and at 30 day Post discharge
Number of readmissions due to ADHF
Measured: Within 30-day post-discharge follow up
Dyspnea assessment by Visual Analog Scale score
Measured: Post infusion, Pre discharge and at 30 day Post discharge
Subjective feeling based on Minnesota - Living with Heart Failure Questionnaire
Measured: Pre-discharge and 30-day post-discharge follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2008 (estimated)
- Study startOct 2008
- Primary completionFeb 2010
- Study completionFeb 2010
Why it stopped: Sponsor support withdrawn
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Albert Einstein Healthcare Network
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma Inc
- Investigators
- Darshak H Karia, MD, Principal investigator, Albert Einstein Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00806910
- Sponsor's protocol ID
- HN-4040
- Status last verified
- Jun 2011
- First submitted
- 10 Dec 2008
- Last updated
- 23 Jun 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Diuretic and Renal Effects of Vaprisol When Administered Along With Furosemide and Nesiritide Continuous Infusion
- ClinicalTrials.gov ID
- NCT00806910
- Acronym / sponsor ID
- HN-4040
- Conditions
- Heart Failure
- Keywords
- Heart Failure, conivaptan, Diuresis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor support withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Albert Einstein Healthcare NetworkUniversity, hospital or other
- Collaborators
- Astellas Pharma Inc
- Study start
- Oct 2008
- Primary completion
- Feb 2010 (actual)
- Study completion
- Feb 2010 (actual)
- First posted
- 11 Dec 2008 (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.
Heart Failure is a growing and challenging public health concern in the United States. Heart failure commonly manifests as a syndrome of salt and water retention. Arginine vasopressin is a peptide hormone that is intimately involved in salt and water homeostasis. AVP is released into the circulation in response low blood volume and hypernatraemia. Despite fluid overload, vasopressin levels are often inappropriately elevated in patients with heart failure and LV dysfunction. Data suggest that vasopressin may also contribute to the deleterious circulatory response in patients with heart failure and play a role in the development and progression of the disease process. In their study, Udelson et al. showed that vasopressin receptor antagonism with Conivaptan resulted in significant diuresis with stable hemodynamics in advanced heart failure patients. Currently Intravenous diuretics and vasodilators are the standard of care in treating patients with acute decompensated heart failure. We will be studying the renal and diuretic effects of add on therapy with intravenous Conivaptan in patients receiving intravenous Nesiritide and intravenous diuretics.
Detailed description
Heart failure effects 5 to 6 million Americans and is increasing in prevalence. There are about 550, 000 new cases of heart failure every year and about 3 million admissions for acute decompensated heart failure every year. The total cost of heat failure on the health systems is upwards of 35 billion dollars per year. Despite advances in medical care, the hospital readmission rate is 20% at one month and 50% at six months. This prevailing situation mandates further exploration of novel therapeutic targets to treat this complex disease.
Vasopressin levels are often elevated in patients with heart failure and LV dysfunction which is paradoxical and inappropriate. It has been hypothesized that high levels of circulating vasopressin may play an important role not only in the pathophysiology of the heart failure syndrome but also contribute to its disease progression.
Studies have shown that Conivaptan, a Vasopressin antagonist results in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. No consensus has been reached for Conivaptan to be used as a sole agent in Acute Decompensated Heart Failure (ADHF) patients and IV loop diuretics and/or vasodilators such as Nesiritide are used as the prime treatment for vascular congestion. This prevailing situation brings the questions whether, Conivaptan can be used as an adjunct to IV Furosemide and/or Nesiritide presenting with ADHF.We intend to investigate this question in a cohort of heart failure patients with hyponatremia.
This study will enroll 60 patients ( who meets all the inclusion criteria and none of the exclusion criteria), admitted to the Albert Einstein Medical Center with the diagnosis of Acute Decompensated Heart Failure (New York Heart Association class 3 and 4). The study population will be divided into 2 groups; a treatment group and a placebo group as described below. Each group will be comprised of 30 patients.
The treatment group will be treated with Nesiritide infusion, intravenous Furosemide (either continuous infusion or bolus injection- total dose of Furosemide received at the end of the study will be calculated) and IV Vaprisol. The placebo group will be given Nesiritide infusion and intravenous Furosemide(either continuous infusion or bolus injection) and placebo. Treatment will be continued in both groups for 24-36 hours.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Active comparator | Drug: ConivaptanSubjects will be treated with Intravenous Vaprisol along with Nesiritide infusion and intravenous Furosemide (either continuous infusion or bolus injections - total dose of Furosemide received will be calculated at the end of the study). |
| Placebo | Placebo comparator | Other: PlaceboSubjects will be given Placebo (at the same rate of Vaprisol given in the treatment arm) along with Nesiritide infusion and intravenous Furosemide (either continuous infusion or bolus injections - total dose of Furosemide received will be calculated at the end of the study). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients over the age of 18 and able to consent
- LVEF ≤40% (as measured within last 6 months before entering into the study)
- Patients with Acute Decompensated Heart Failure (ADHF) (NYHA class 3 \& 4)
- Patients with estimated GFR >40ml/min as calculated by Cockcroft-Gault or MDRD formula
- Serum Sodium level <135 meq/L
Key exclusion criteria (27 listed)
- Patients with Acute Coronary Syndrome (ACS: Unstable angina, NSTEMI or STEMI)
- Patients on pressors (including Vasopressin analogs) for hemodynamic stability
- Supine systolic blood pressure <100 mm Hg
- Hypersensitivity to Conivaptan
- Concomitant use of medications that affects hepatic drug metabolism (e.g. Ketoconazole, Itraconazole, Ritonavir, Indinavir, Clarithromycin etc.)
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 |
|---|---|---|
| ConivaptanAlso: VaprisolIV Vaprisol initially at 20 mg IV injection over 30 minutes, followed by a 20 mg IV infusion over the next 24 hours (i.e. 20 mg bolus, 20 mg continuous infusion approximately 24 hrs). | Drug | Treatment |
| PlaceboAlso: SalinePlacebo (will be given at the same rate of Vaprisol given in the treatment arm) | Other | Placebo |
Primary outcome
Degree of diuresis as measured by weight change and intake and output measurement
Time frame: Post infusion, Pre discharge and at 30 day Post discharge
7 secondary outcomes
Length of stay (LOS) in hospital
Time frame: Concurrent
Clinical status based on NYHA criteria
Time frame: Pre-discharge and 30-day post-discharge follow up
Serum electrolytes
Time frame: Pre and Post infusion
BUN and Serum Creatinine concentration
Time frame: Post infusion, Pre discharge and at 30 day Post discharge
Number of readmissions due to ADHF
Time frame: Within 30-day post-discharge follow up
Dyspnea assessment by Visual Analog Scale score
Time frame: Post infusion, Pre discharge and at 30 day Post discharge
Subjective feeling based on Minnesota - Living with Heart Failure Questionnaire
Time frame: Pre-discharge and 30-day post-discharge follow up
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2011.
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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.
Darshak H Karia, MD principal investigator
Albert Einstein Medical Center
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Conivaptan in people with Heart Failure, run by Albert Einstein Healthcare Network.
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 7 inclusion and 27 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: withdrawn, as of the sponsor's last update on 23 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 withdrawn before enrolling participants, so there are no results.
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?
Degree of diuresis as measured by weight change and intake and output measurement (time frame: Post infusion, Pre discharge and at 30 day Post discharge). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Jun 2011.