Chronic Kidney DiseasePhase 4DOCKNCT04192110
Association of Diuretics With Change in Extracellular Volume, Natriuretic Peptides, Symptoms, and Cardiovascular Outcomes in CKD
A Phase 4 study testing Diuretic initiation or augmentation in people with Chronic Kidney Disease, run by VA Office of Research and Development at 1 site in United States.
Trial summary
Almost 15% of Americans have chronic kidney disease (CKD), with an even higher rate in Veterans due to common risk factors such as high blood pressure and diabetes. People with CKD have a high risk of cardiovascular (CV) diseases, such as heart attacks, heart failure, and strokes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Kidney Disease
- What is being tested?
- Diuretic initiation or augmentation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Aug 2020to 11 Aug 2020
- 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
- The presence of CKD stages 1, 2, or 3, as defined below by National Kidney Foundation guidelines, for a period of at least 3 months.
- Stage 1: eGFR 90 mL/min/1.73 m2 and spot urine albumin-to-creatinine ratio 30 mg/g.
- Stage 2: eGFR 60-89 mL/min/1.73 m2 and spot urine albumin-to-creatinine ratio 30 mg/g.
- Stage 3: eGFR 30-59 mL/min/1.73 m2.
- Measured blood pressure either >140 mmHg systolic or >90 mmHg diastolic at the two most recent clinic visits.
- Rationale: The investigators' unpublished preliminary data show that blood pressure correlates with both BNP and NT-pro-BNP more strongly in those with CKD than those without CKD. Thus, selecting hypertensive individuals is more likely to identify those with elevated natriuretic peptides in the CKD group.
- Furthermore, starting or increasing a diuretic medication is part of standard of care to treat blood pressures >140/90 mmHg, so the study intervention will be consistent with appropriate care for the Veteran and avoid hypotension.
- Able to understand and sign informed consent after the nature of the study has been fully explained.
Who cannot join
- Unable to understand or provide informed consent.
- Unwilling or unable to participate in the protocol or comply with any of its components.
- CKD stages 4-5, defined as eGFR <30 mL/min/1.73 m2.
- Receiving chronic hemodialysis or peritoneal dialysis.
- Recipient of a kidney transplant.
- Serum potassium <3.5 mg/dL at baseline.
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- Known left ventricular ejection fraction <40% on visual estimate based on chart review of available echocardiogram data.
- Known hepatic cirrhosis.
- Major limb amputation.
- Known pregnancy.
- Presence of a pacemaker or defibrillator.
- Presence of metal prostheses.
Trial locations and contacts
1 site in 1 country.
United States1 site
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
Dallas, Texas, 75216
About this study
Almost 15% of Americans have chronic kidney disease (CKD), with an even higher rate in Veterans due to common risk factors such as high blood pressure and diabetes. People with CKD have a high risk of cardiovascular (CV) diseases, such as heart attacks, heart failure, and strokes. Extra fluid in the body, called volume overload, may lead to CV disease in people with CKD. It is unknown if volume overload develops in the earliest stages of CKD, when treating it with common, inexpensive medicines called diuretics may improve long-term CV outcomes. This study will lay important groundwork to answer this question in Veterans with early CKD by comparing two ways to measure volume overload and studying the change in common symptoms like fatigue and short-term CV function after treatment with diuretic medicines.
Read the detailed description
The investigators previously showed that brain natriuretic peptide (BNP) and N-terminal-pro-BNP (NT-pro-BNP), measures of ventricular stretch, are associated with death and cardiovascular (CV) outcomes in chronic kidney disease (CKD) stages 1-3 patients, and the investigators' preliminary pilot results suggest that these natriuretic peptides may correlate with objective measures of excess extracellular volume (ECV) and with symptoms common in CKD. The overarching objective is to determine if initiation of diuretic treatment or increase in dose is associated with changes in BNP and NT-pro-BNP, patient-reported symptom burden, and short-term hemodynamic parameters in patients with CKD stages 1-3 and elevated blood pressure, and whether these changes correlate with changes in ECV. The central hypothesis is that the change in ECV after starting or increasing diuretics in Veterans with stages 1-3 CKD is associated with changes in 1) natriuretic peptides, 2) patient-level factors, and 3) CV physiology.
The investigators will compare the changes in natriuretic peptides, symptoms, and CV parameters with the change in ECV after diuretic initiation or dose increase. The primary aim is to determine if initiation of diuretic treatment or increase in diuretic dose is associated with changes in natriuretic peptides. Secondary aims are to determine the effect of diuretic change on patient-reported symptom burden, and CV physiology.
This clinical trial will include 46 outpatients with CKD stages 1-3 and blood pressure >140/90 mmHg. At the first visit, I will initiate or increase the dose of a thiazide or loop diuretic. Study measures other than echocardiogram will be repeated 4 weeks after the intervention to determine changes in these parameters. ECV will be measured by whole-body multifrequency bioimpedance spectroscopy (BIS), which is a validated, non-invasive, painless measure of ECV. Plasma BNP and NT-pro-BNP will be measured, and patient-reported fatigue, depression, and quality of life will be quantified using validated questionnaires. Hemodynamic parameters include blood pressure, pulse pressure, total peripheral resistance index (TPRI), and cardiac index measured by Non-Invasive Cardiac Output Monitoring. A transthoracic echocardiogram will measure left ventricular mass index, valvular disease, and diastolic dysfunction.
Variables will be compared within participants between baseline and Visit 2 using paired Wilcoxon Signed Rank tests or paired Student's t tests, depending on variable distributions. Correlations between change in ECV/total body weight and all continuous outcome measures will be analyzed using Spearman or Pearson correlations, applying appropriate transformations. Linear regression analysis will control for clinically relevant variables. The relationship between ECV/total body weight and natriuretic peptides from both visits will be evaluated using a mixed effects model to account for the change in these measures between baseline and Visit 2.
This study is minimal risk to human subjects. Participants may benefit from improved control of their blood pressure. The knowledge to be gained may also benefit others in the future.
- Conditions
- Chronic Kidney Disease
- Being tested
- Diuretic initiation or augmentation
- Keywords
- Chronic kidney disease, Diuretics, Volume overload, Natriuretic peptides, Bioimpedance spectroscopy, Cardiovascular disease
- Medical subject headings
- Renal Insufficiency, Chronic, Edema, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diuretic initiation or augmentationDrug
The participant's blood pressure medication regimen will then be altered to initiate a thiazide-type (hydrochlorothiazide or chlorthalidone) or loop diuretic (furosemide, bumetanide, or torsemide) in those not already prescribed a diuretic, or to increase the dose if one is already prescribed
| Study group | Role | What they receive |
|---|---|---|
| Diuretic initiation or augmentation | Experimental | Participants will either initiate or increase the dose of a loop or thiazide-type diuretic Receives: Drug: Diuretic initiation or augmentation |
What is being measured
The primary outcome is the main question the study is designed to answer.
NT-pro-BNP
Change from baseline to 4 weeks in NT-pro-BNP
Measured: 4 weeks
Total peripheral resistance index
The change from baseline to 4 weeks in total peripheral resistance index will be measured using Non-Invasive Cardiac Output Monitoring (Cheetah)
Measured: 4 weeks
Secondary outcomes (10)
BNP
Change from baseline to 4 weeks in BNP
Measured: 4 weeks
Fatigue
The change in fatigue from baseline to 4 weeks, measured by the Functional Assessment of Chronic Illness Therapy - Fatigue, a validated measure of patient-reported fatigue
Measured: 4 weeks
Depression
The change in depressive symptoms from baseline to 4 weeks, measured by the Quick Inventory of Depressive Symptomatology, a validated measure of patient-reported depression
Measured: 4 weeks
Quality of Life - Kidney Disease Quality of Life (KDQOL)
The change in quality of life from baseline to 4 weeks, measured by the KDQOL, a validated measure of patient-reported quality of life
Measured: 4 weeks
Hospitalizations
Hospitalizations as quantified by review of the medical record and telephone contact with the participant
Measured: 6 months
Systolic blood pressure
The change in systolic blood pressure from baseline to 4 weeks
Measured: 4 weeks
Diastolic blood pressure
The change in diastolic blood pressure from baseline to 4 weeks
Measured: 4 weeks
Mean arterial blood pressure
The change in mean arterial blood pressure from baseline to 4 weeks
Measured: 4 weeks
Pulse pressure
The change in pulse pressure from baseline to 4 weeks
Measured: 4 weeks
Cardiac index
The change from baseline to 4 weeks in cardiac index will be measured using Non-Invasive Cardiac Output Monitoring (Cheetah)
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2019
- Study start11 Aug 2020
- Primary completion11 Aug 2020
- Study completion11 Aug 2020
Why it stopped: The project has ended prior to beginning.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single group open label initiation or dose increase of loop or thiazide-type diuretics
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Lucile P Gregg, MD, Principal investigator, VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04192110
- Sponsor's protocol ID
- NEPH-025-19S
- Other IDs
- 1IK2CX002030-01
- Acronym
- DOCK
- Status last verified
- Dec 2021
- First submitted
- 6 Dec 2019
- Last updated
- 9 Dec 2021
- Results posted
- No
- 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 9 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Association of Diuretics With Change in Extracellular Volume, Natriuretic Peptides, Symptoms, and Cardiovascular Outcomes in CKD
- ClinicalTrials.gov ID
- NCT04192110
- Acronym / sponsor ID
- DOCK / NEPH-025-19S
- Conditions
- Chronic Kidney Disease
- Keywords
- Chronic kidney disease, Diuretics, Volume overload, Natriuretic peptides, Bioimpedance spectroscopy, Cardiovascular disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The project has ended prior to beginning.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 11 Aug 2020 (actual)
- Primary completion
- 11 Aug 2020 (actual)
- Study completion
- 11 Aug 2020 (actual)
- First posted
- 10 Dec 2019 (actual)
- 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.
Almost 15% of Americans have chronic kidney disease (CKD), with an even higher rate in Veterans due to common risk factors such as high blood pressure and diabetes. People with CKD have a high risk of cardiovascular (CV) diseases, such as heart attacks, heart failure, and strokes. Extra fluid in the body, called volume overload, may lead to CV disease in people with CKD. It is unknown if volume overload develops in the earliest stages of CKD, when treating it with common, inexpensive medicines called diuretics may improve long-term CV outcomes. This study will lay important groundwork to answer this question in Veterans with early CKD by comparing two ways to measure volume overload and studying the change in common symptoms like fatigue and short-term CV function after treatment with diuretic medicines.
Detailed description
The investigators previously showed that brain natriuretic peptide (BNP) and N-terminal-pro-BNP (NT-pro-BNP), measures of ventricular stretch, are associated with death and cardiovascular (CV) outcomes in chronic kidney disease (CKD) stages 1-3 patients, and the investigators' preliminary pilot results suggest that these natriuretic peptides may correlate with objective measures of excess extracellular volume (ECV) and with symptoms common in CKD. The overarching objective is to determine if initiation of diuretic treatment or increase in dose is associated with changes in BNP and NT-pro-BNP, patient-reported symptom burden, and short-term hemodynamic parameters in patients with CKD stages 1-3 and elevated blood pressure, and whether these changes correlate with changes in ECV. The central hypothesis is that the change in ECV after starting or increasing diuretics in Veterans with stages 1-3 CKD is associated with changes in 1) natriuretic peptides, 2) patient-level factors, and 3) CV physiology.
The investigators will compare the changes in natriuretic peptides, symptoms, and CV parameters with the change in ECV after diuretic initiation or dose increase. The primary aim is to determine if initiation of diuretic treatment or increase in diuretic dose is associated with changes in natriuretic peptides. Secondary aims are to determine the effect of diuretic change on patient-reported symptom burden, and CV physiology.
This clinical trial will include 46 outpatients with CKD stages 1-3 and blood pressure >140/90 mmHg. At the first visit, I will initiate or increase the dose of a thiazide or loop diuretic. Study measures other than echocardiogram will be repeated 4 weeks after the intervention to determine changes in these parameters. ECV will be measured by whole-body multifrequency bioimpedance spectroscopy (BIS), which is a validated, non-invasive, painless measure of ECV. Plasma BNP and NT-pro-BNP will be measured, and patient-reported fatigue, depression, and quality of life will be quantified using validated questionnaires. Hemodynamic parameters include blood pressure, pulse pressure, total peripheral resistance index (TPRI), and cardiac index measured by Non-Invasive Cardiac Output Monitoring. A transthoracic echocardiogram will measure left ventricular mass index, valvular disease, and diastolic dysfunction.
Variables will be compared within participants between baseline and Visit 2 using paired Wilcoxon Signed Rank tests or paired Student's t tests, depending on variable distributions. Correlations between change in ECV/total body weight and all continuous outcome measures will be analyzed using Spearman or Pearson correlations, applying appropriate transformations. Linear regression analysis will control for clinically relevant variables. The relationship between ECV/total body weight and natriuretic peptides from both visits will be evaluated using a mixed effects model to account for the change in these measures between baseline and Visit 2.
This study is minimal risk to human subjects. Participants may benefit from improved control of their blood pressure. The knowledge to be gained may also benefit others in the future.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single group open label initiation or dose increase of loop or thiazide-type diuretics
| Arm | Type | Receives |
|---|---|---|
| Diuretic initiation or augmentation | Experimental | Drug: Diuretic initiation or augmentationParticipants will either initiate or increase the dose of a loop or thiazide-type diuretic |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- The presence of CKD stages 1, 2, or 3, as defined below by National Kidney Foundation guidelines, for a period of at least 3 months.
- Measured blood pressure either >140 mmHg systolic or >90 mmHg diastolic at the two most recent clinic visits.
- Able to understand and sign informed consent after the nature of the study has been fully explained.
Key exclusion criteria (12 listed)
- Unable to understand or provide informed consent.
- Unwilling or unable to participate in the protocol or comply with any of its components.
- CKD stages 4-5, defined as eGFR <30 mL/min/1.73 m2.
- Receiving chronic hemodialysis or peritoneal dialysis.
- Recipient of a kidney transplant.
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 |
|---|---|---|
| Diuretic initiation or augmentationThe participant's blood pressure medication regimen will then be altered to initiate a thiazide-type (hydrochlorothiazide or chlorthalidone) or loop diuretic (furosemide, bumetanide, or torsemide) in those not already prescribed a diuretic, or to increase the dose if one is already prescribed | Drug | Diuretic initiation or augmentation |
Primary outcome
NT-pro-BNP
Time frame: 4 weeks
Change from baseline to 4 weeks in NT-pro-BNP
Total peripheral resistance index
Time frame: 4 weeks
The change from baseline to 4 weeks in total peripheral resistance index will be measured using Non-Invasive Cardiac Output Monitoring (Cheetah)
10 secondary outcomes
BNP
Time frame: 4 weeks
Fatigue
Time frame: 4 weeks
Depression
Time frame: 4 weeks
Quality of Life - Kidney Disease Quality of Life (KDQOL)
Time frame: 4 weeks
Hospitalizations
Time frame: 6 months
Systolic blood pressure
Time frame: 4 weeks
Diastolic blood pressure
Time frame: 4 weeks
Mean arterial blood pressure
Time frame: 4 weeks
Pulse pressure
Time frame: 4 weeks
Cardiac index
Time frame: 4 weeks
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 9 Dec 2021.
- 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.
Lucile P Gregg, MD principal investigator
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
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 Diuretic initiation or augmentation in people with Chronic Kidney Disease, run by VA Office of Research and Development 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 8 inclusion and 12 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 9 Dec 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. 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?
NT-pro-BNP (time frame: 4 weeks). 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 9 Dec 2021.