Cardiorenal Syndrome (CRS)Phase 1/2NCT01678794
CR Aim #2 - AT1 Receptor Blockade & ACE Inhibition Effect on Humoral Function
A Phase 1/2 study testing Candesartan in people with Cardiorenal Syndrome (CRS), run by Mayo Clinic at 1 site in United States.
Trial summary
To advance our understanding of the mechanisms of human cardiorenal syndrome with emphasis upon the interaction of diuretic therapy and the renal-angiotensin-aldosterone -system and cGMP pathway. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiorenal Syndrome (CRS)
- What is being tested?
- Candesartan
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2012to 29 Jun 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Left ventricular ejection fraction of equal or less than 40% assessed by echocardiography, nuclear scan, MRI or left ventriculogram within the past 48 months.
- Stable New York Heart Association (NYHA) class II and III symptoms as defined by: no change in NYHA symptoms over the past 3 months, on stable doses of ACE inhibitor, beta blocker, digoxin and furosemide over the last 4 weeks and no episode of decompensated CHF over the past 6 months.
- Calculated creatinine clearance of equal or less than 80 ml/min and greater than 20 ml/min, using the MDRD formula assessed within the past 48 months and a confirmatory calculated creatinine clearance equal or less than 80 ml/min and greater than 20 ml/min at the time of enrollment.
- Subjects who are already taking AT1 receptor blocker will be excluded. Aldosterone antagonist, antiarrhythmic medications and other vasodilators will be allowed; however, all medications must be at stable doses 4 weeks prior to enrollment. Subjects taking nonsteroidal anti-inflammatory drugs (NSAIDs) except aspirin will not be able to increase their medication dose for the duration of the study. Subjects will be excluded if they have had a prior diagnosis of intrinsic renal disease, including renal artery stenosis of > 50%, or if they meet any one of the exclusion criteria listed below.
Who cannot join
- Prior diagnosis of intrinsic renal diseases including renal artery stenosis of > 50%
- Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period
- Hospitalization for decompensated CHF during the past 6 months
- Subjects that are taking AT1 receptor blockers
- Myocardial infarction within 6 months of screening
- Unstable angina within 6 months of screening, or any evidence of myocardial ischemia
Show all 21Show fewer
- Significant valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis
- Severe congenital heart diseases
- Sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening
- Second or third degree heart block without a permanent cardiac pacemaker
- Stroke within 3 months of screening, or other evidence of significantly compromised CNS perfusion
- ALT >1.5 times the upper limit of normal
- Serum sodium of < 125 mEq/dL or > 160 mEq/dL
- Serum potassium of < 3.5 mEq/dL or > 5.7 mEq/dL
- Serum digoxin level of > 2.0 ng/ml
- Hemoglobin < 9 gm/dl
- Other acute or chronic medical conditions or laboratory abnormality which may increase the risks associated with study participation or may interfere with interpretation of the data
- Received an investigational drug within 1 month prior to dosing
- Patients with an allergy to iodine.
- Female subject who is pregnant or breastfeeding
- In the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any reasons
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Define in Humans With Compensated CHF and Renal Dysfunction, the Modulating Action of Chronic AT1 Receptor Blockade in Addition to ACE Inhibition on Cardiorenal and Humoral Function
To advance our understanding of the mechanisms of human cardiorenal syndrome with emphasis upon the interaction of diuretic therapy and the renal-angiotensin-aldosterone -system and cGMP pathway.
The belief is that the chronic AT1 receptor blockade in subjects with compensated CHF and renal dysfunction will improve renal function with increased sodium excretion, glomerular filtration rate and effective renal plasma flow and renal function reserve as compared to the response of placebo-treated subjects.
Read the detailed description
IRB # 09-003284, "Specific Aims 2: Define in humans with compensated CHF and renal dysfunction, the modulating action of chronic AT1 receptor blockade in addition to ACE inhibition on cardiorenal and humoral function", involving 12 weeks of study drug (Candesartan or placebo) starting at 4 mg daily and doubling every 2 weeks to 16 mg, if tolerated. Safety labs are performed one week after each dose increase (end of weeks 1, 3 and 5), and in week 10 of the study. Participants are monitoring their blood pressure weekly, and are aware to watch for symptoms of hypotension (lightheadedness, dizziness, blurred vision). Renal clearance testing and ECHO are performed at the start and end of the 12 weeks of study medication in the 5-Domitilla Clinical Research Unit.
- Conditions
- Cardiorenal Syndrome (CRS)
- Being tested
- Candesartan, Placebo
- Keywords
- Chronic heart failure (CHF), cardiac and renal dysfunction
- Medical subject headings
- Cardio-Renal Syndrome, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CandesartanDrug
Also called Atacand
4 mg once a day up to 13 day. dose will be doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated
PlaceboDrug
4 mg once a day up to 13 day. dose will be doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated
| Study group | Role | What they receive |
|---|---|---|
| Candesartan | Experimental | Not described Receives: Drug: Candesartan |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Glomerular Filtration Rate
Glomerular Filtration Rate estimates how much blood passes through the glomeruli each minute. Glomeruli are the tiny filters in the kidneys that filter waste from the blood. Measured as ml/min/1.73 m2
Measured: baseline to 3 months
Change in Urinary Sodium Excretion
Urinary sodium excretion correlates with elevated blood pressure in subjects at low cardiovascular risk. The body continually monitors blood volume and sodium concentration. When either becomes too high, sensors in the heart, blood vessels, and kidneys detect the increases and stimulate the kidneys to increase sodium excretion, thus returning blood volume to normal. Measured as mEq/min
Measured: baseline to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2012 (estimated)
- Study startFeb 2012
- Primary completion29 Jun 2016
- Study completion29 Jun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cardiorenal Syndrome (CRS)Studies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Horng Chen, Mayo Clinic
- Investigators
- Horng H. Chen, M.D., Principal investigator, Mayo Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01678794
- Sponsor's protocol ID
- 09-003284
- Other IDs
- 1R01HL084155-01A2
- Status last verified
- Oct 2021
- First submitted
- 31 Aug 2012
- Last updated
- 18 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Define in Humans With Compensated CHF and Renal Dysfunction, the Modulating Action of Chronic AT1 Receptor Blockade in Addition to ACE Inhibition on Cardiorenal and Humoral Function
- ClinicalTrials.gov ID
- NCT01678794
- Acronym / sponsor ID
- 09-003284
- Conditions
- Cardiorenal Syndrome (CRS)
- Keywords
- Chronic heart failure (CHF), cardiac and renal dysfunction
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Feb 2012
- Primary completion
- 29 Jun 2016 (actual)
- Study completion
- 29 Jun 2016 (actual)
- First posted
- 5 Sep 2012 (estimated)
- Results
- Posted 18 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To advance our understanding of the mechanisms of human cardiorenal syndrome with emphasis upon the interaction of diuretic therapy and the renal-angiotensin-aldosterone -system and cGMP pathway.
The belief is that the chronic AT1 receptor blockade in subjects with compensated CHF and renal dysfunction will improve renal function with increased sodium excretion, glomerular filtration rate and effective renal plasma flow and renal function reserve as compared to the response of placebo-treated subjects.
Detailed description
IRB # 09-003284, "Specific Aims 2: Define in humans with compensated CHF and renal dysfunction, the modulating action of chronic AT1 receptor blockade in addition to ACE inhibition on cardiorenal and humoral function", involving 12 weeks of study drug (Candesartan or placebo) starting at 4 mg daily and doubling every 2 weeks to 16 mg, if tolerated. Safety labs are performed one week after each dose increase (end of weeks 1, 3 and 5), and in week 10 of the study. Participants are monitoring their blood pressure weekly, and are aware to watch for symptoms of hypotension (lightheadedness, dizziness, blurred vision). Renal clearance testing and ECHO are performed at the start and end of the 12 weeks of study medication in the 5-Domitilla Clinical Research Unit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Candesartan | Experimental | Drug: Candesartan |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Left ventricular ejection fraction of equal or less than 40% assessed by echocardiography, nuclear scan, MRI or left ventriculogram within the past 48 months.
- Stable New York Heart Association (NYHA) class II and III symptoms as defined by: no change in NYHA symptoms over the past 3 months, on stable doses of ACE inhibitor, beta blocker, digoxin and furosemide over the last 4 weeks and no episode of decompensated CHF over the past 6 months.
- Calculated creatinine clearance of equal or less than 80 ml/min and greater than 20 ml/min, using the MDRD formula assessed within the past 48 months and a confirmatory calculated creatinine clearance equal or less than 80 ml/min and greater than 20 ml/min at the time of enrollment.
- Subjects who are already taking AT1 receptor blocker will be excluded. Aldosterone antagonist, antiarrhythmic medications and other vasodilators will be allowed; however, all medications must be at stable doses 4 weeks prior to enrollment. Subjects taking nonsteroidal anti-inflammatory drugs (NSAIDs) except aspirin will not be able to increase their medication dose for the duration of the study. Subjects will be excluded if they have had a prior diagnosis of intrinsic renal disease, including renal artery stenosis of > 50%, or if they meet any one of the exclusion criteria listed below.
Key exclusion criteria (21 listed)
- Prior diagnosis of intrinsic renal diseases including renal artery stenosis of > 50%
- Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period
- Hospitalization for decompensated CHF during the past 6 months
- Subjects that are taking AT1 receptor blockers
- Myocardial infarction within 6 months of screening
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 |
|---|---|---|
| CandesartanAlso: Atacand4 mg once a day up to 13 day. dose will be doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated | Drug | Candesartan |
| Placebo4 mg once a day up to 13 day. dose will be doubled every 14-18 days as tolerated to a goal of 16 mg a day or highest dose tolerated | Drug | Placebo |
Primary outcome
Change in Glomerular Filtration Rate
Time frame: baseline to 3 months
Glomerular Filtration Rate estimates how much blood passes through the glomeruli each minute. Glomeruli are the tiny filters in the kidneys that filter waste from the blood. Measured as ml/min/1.73 m2
Change in Urinary Sodium Excretion
Time frame: baseline to 3 months
Urinary sodium excretion correlates with elevated blood pressure in subjects at low cardiovascular risk. The body continually monitors blood volume and sodium concentration. When either becomes too high, sensors in the heart, blood vessels, and kidneys detect the increases and stimulate the kidneys to increase sodium excretion, thus returning blood volume to normal. Measured as mEq/min
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Horng H. Chen, M.D. principal investigator
Mayo Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Candesartan in people with Cardiorenal Syndrome (CRS), run by Mayo Clinic at 1 site in United States.
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 4 inclusion and 21 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 18 Nov 2021. 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 United States. 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. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Glomerular Filtration Rate (time frame: baseline to 3 months). 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 18 Nov 2021.