Heart Failure, CongestivePhase 3REACH UPNCT00443690
Placebo-Controlled Randomized Study of KW-3902 for Subjects Hospitalized With Worsening Renal Function and Heart Failure Requiring IV Therapy
A Phase 3 study testing rolofylline in people with Heart Failure, Congestive, run by NovaCardia, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).
Trial summary
To evaluate the effect of KW-3902IV, in addition to standard therapy, on the proportion of worsening heart failure and worsening renal function, and on the proportion of deaths or rehospitalizations for heart failure or worsening renal function, and to estimate and compare within-trial medical resource utilization and… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Congestive
- What is being tested?
- rolofylline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 480 participants
- Where
- No sites listed yet
- Study dates
- Aug 2007to Jan 2009
- Phase
- Phase 3
- 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
- Dyspnea at rest or with minimal exertion at randomization
- Fluid overload
- Estimated creatinine clearance (CrCl) between 20-60 mL/min
- Worsening renal function
- Anticipated need for IV diuretic treatment for at least 48 hours after the start of study drug
- BNP >500 pg/mL or NT-pro-BNP >2000 pg/mL
- Systolic blood pressure ≥90 mmHg at randomization
Who cannot join
- IV radiographic contrast within 14 days
- IV vasodilators within 6 hours
- Serum potassium <3.5 meq/L
- Ongoing or planned therapy for heart failure with mechanical circulatory or ventilatory support
- Ongoing or planned treatment with ultrafiltration, hemofiltration, or dialysis
- Rapidly progressive acute renal failure
Show all 31Show fewer
- Evidence of acute tubular necrosis or post-obstructive nephropathy or other exogenous causes of acute kidney injury, unrelated to heart failure
- Severe pulmonary disease
- Significant stenotic mitral or aortic valvular disease
- Heart transplant recipient or admitted for cardiac transplantation or LVAD surgery
- Any major surgery within 2 weeks prior
- evidence of acute coronary syndrome in the 2 weeks prior
- Hgb <8 g/dL, Hct <25%, or active bleeding requiring transfusion
- Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy.
- Known hepatic impairment
- Non-cardiac pulmonary edema
- Temperature >38°C
- Sepsis or active infection requiring IV anti-microbial treatment
- Administration of an investigational drug or device within 30 days
- Current or anticipated therapy with atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole
- Administration of any vasopressor or inotropic drug within 72 hours
- History of seizure (except febrile seizure)
- Stroke within 2 years
- History of brain tumor of any etiology
- Brain surgery within 2 years
- Encephalitis/meningitis within 2 years
- History of penetrating head trauma
- Closed head injury with loss of consciousness (LOC) over 30 minutes within 2 years
- History of or at risk for alcohol withdrawal seizures
- Advanced Alzheimer's disease
- Advanced multiple sclerosis
About this study
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Effects of KW-3902 Injectable Emulsion on Heart Failure Signs and Symptoms, Diuresis, Renal Function, and Clinical Outcomes in Subjects Hospitalized With Worsening Renal Function and Heart Failure Requiring Intravenous Therapy
To evaluate the effect of KW-3902IV, in addition to standard therapy, on the proportion of worsening heart failure and worsening renal function, and on the proportion of deaths or rehospitalizations for heart failure or worsening renal function, and to estimate and compare within-trial medical resource utilization and direct medical costs between subjects treated with KW 3902IV versus placebo.
Read the detailed description
Loop diuretics are generally first line therapy in patients hospitalized with acute heart failure syndrome (AHFS). Their use far exceeds that of vasoactive agents. Tubuloglomerular feedback (TGF) is the body's compensatory response to avoid excess fluid loss, and it is activated when elevated sodium concentrations in the distal tubule are detected. TGF is proposed as a contributing factor for the observed diuretic resistance that occurs in patients with heart failure. Higher doses of diuretics are required to overcome the decreased natriuresis and reduced RBF induced by TGF. Ultimately, this action creates a vicious cycle of worsening renal function and diminished diuretic effectiveness.
The primary pharmacologic rationale for the use of KW-3902 in subjects with AHFS is its mechanism of action as an adenosine A1 receptor antagonist. TGF promotes release of adenosine, and adenosine binding to A1 receptors causes vasoconstriction of the afferent arteriole, decreased RBF, and enhanced sodium reabsorption by the proximal tubule. This action results in a decrease in GFR, diminished renal function, and sodium and water retention. Blocking adenosine A1 receptors via a selective adenosine receptor antagonist may limit sodium reabsorption by the proximal tubules without triggering TGF. It promotes vasodilation of the afferent arteriole of the glomerulus, and thus, this strategy offers the potential to overcome diuretic resistance or enhance diuretic responsiveness. It may also reduce the need for increasing diuretic doses that have been associated with worse outcomes.
- Conditions
- Heart Failure, Congestive
- Being tested
- rolofylline, Comparator: Placebo (unspecified)
- Keywords
- heart failure, diuretic, renal impairment, renal function
- Medical subject headings
- Heart Failure, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rolofyllineDrug
Also called KW-3902IV, MK7418
rolofylline 30 mg IV QD; 3 days
Comparator: Placebo (unspecified)Drug
rolofylline Pbo 30 mg IV QD; 3 days
| Study group | Role | What they receive |
|---|---|---|
| 2 | Placebo comparator | placebo control Receives: Drug: Comparator: Placebo (unspecified) |
| 1 | Experimental | KW-3902IV Receives: Drug: rolofylline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect on heart failure signs and symptoms
Measured: through day 7
Effect on renal function
Measured: through Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2007 (estimated)
- Study startAug 2007
- Primary completionJan 2009
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure, CongestiveStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 480 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NovaCardia, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Investigators
- Barry Massie, MD, Study chair, University of California San Francisco, USAChristopher O'Connor, MD, Study chair, Duke University, USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00443690
- Sponsor's protocol ID
- CKI-303
- Other IDs
- 2007_805, MK7418-303
- Acronym
- REACH UP
- Status last verified
- Feb 2009
- First submitted
- 2 Mar 2007
- Last updated
- 20 Feb 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Effects of KW-3902 Injectable Emulsion on Heart Failure Signs and Symptoms, Diuresis, Renal Function, and Clinical Outcomes in Subjects Hospitalized With Worsening Renal Function and Heart Failure Requiring Intravenous Therapy
- ClinicalTrials.gov ID
- NCT00443690
- Acronym / sponsor ID
- REACH UP / CKI-303
- Conditions
- Heart Failure, Congestive
- Keywords
- heart failure, diuretic, renal impairment, renal function
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 480 participants (estimated)
- Lead sponsor
- NovaCardia, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Aug 2007
- Primary completion
- Jan 2009 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 6 Mar 2007 (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.
To evaluate the effect of KW-3902IV, in addition to standard therapy, on the proportion of worsening heart failure and worsening renal function, and on the proportion of deaths or rehospitalizations for heart failure or worsening renal function, and to estimate and compare within-trial medical resource utilization and direct medical costs between subjects treated with KW 3902IV versus placebo.
Detailed description
Loop diuretics are generally first line therapy in patients hospitalized with acute heart failure syndrome (AHFS). Their use far exceeds that of vasoactive agents. Tubuloglomerular feedback (TGF) is the body's compensatory response to avoid excess fluid loss, and it is activated when elevated sodium concentrations in the distal tubule are detected. TGF is proposed as a contributing factor for the observed diuretic resistance that occurs in patients with heart failure. Higher doses of diuretics are required to overcome the decreased natriuresis and reduced RBF induced by TGF. Ultimately, this action creates a vicious cycle of worsening renal function and diminished diuretic effectiveness.
The primary pharmacologic rationale for the use of KW-3902 in subjects with AHFS is its mechanism of action as an adenosine A1 receptor antagonist. TGF promotes release of adenosine, and adenosine binding to A1 receptors causes vasoconstriction of the afferent arteriole, decreased RBF, and enhanced sodium reabsorption by the proximal tubule. This action results in a decrease in GFR, diminished renal function, and sodium and water retention. Blocking adenosine A1 receptors via a selective adenosine receptor antagonist may limit sodium reabsorption by the proximal tubules without triggering TGF. It promotes vasodilation of the afferent arteriole of the glomerulus, and thus, this strategy offers the potential to overcome diuretic resistance or enhance diuretic responsiveness. It may also reduce the need for increasing diuretic doses that have been associated with worse outcomes.
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 |
|---|---|---|
| 2 | Placebo comparator | Drug: Comparator: Placebo (unspecified)placebo control |
| 1 | Experimental | Drug: rolofyllineKW-3902IV |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Dyspnea at rest or with minimal exertion at randomization
- Fluid overload
- Estimated creatinine clearance (CrCl) between 20-60 mL/min
- Worsening renal function
- Anticipated need for IV diuretic treatment for at least 48 hours after the start of study drug
Key exclusion criteria (31 listed)
- IV radiographic contrast within 14 days
- IV vasodilators within 6 hours
- Serum potassium <3.5 meq/L
- Ongoing or planned therapy for heart failure with mechanical circulatory or ventilatory support
- Ongoing or planned treatment with ultrafiltration, hemofiltration, or dialysis
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 |
|---|---|---|
| rolofyllineAlso: KW-3902IV, MK7418rolofylline 30 mg IV QD; 3 days | Drug | 1 |
| Comparator: Placebo (unspecified)rolofylline Pbo 30 mg IV QD; 3 days | Drug | 2 |
Primary outcome
Effect on heart failure signs and symptoms
Time frame: through day 7
Effect on renal function
Time frame: through Day 7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2009.
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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.
Barry Massie, MD study chair
University of California San Francisco, USA
Christopher O'Connor, MD study chair
Duke University, USA
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing rolofylline in people with Heart Failure, Congestive, run by NovaCardia, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).
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 31 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: finished, as of the sponsor's last update on 20 Feb 2009. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Effect on heart failure signs and symptoms (time frame: through day 7). The study lists 2 primary outcomes in all. 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 20 Feb 2009.