Heart FailureNCT04111094
DKK3 for Prognosis and Monitoring of GFR Decline in Heart Failure
An observational study of Heart Failure and Chronic Kidney Diseases, run by University of Giessen at 1 site in Germany.
Trial summary
The individual course of chronic kidney disease (CKD) may vary, and improved methods for identifying which patients will experience estimated glomerular filtration rate (eGFR) decline are needed. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Chronic Kidney Diseases
- How many people
- 290 participants
- Where
- 1 siteGermany
- Study dates
- 14 Oct 2019to 6 May 2024
- Phase
- Observational
- 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
Study population: Outpatients ≥18 years of age with diagnosed HF or diabetes or hypertension or other etiologies of CKD
Who may be able to join
- Outpatients ≥18 years of age with diagnosed HF or diabetes or hypertension
Who cannot join
- CKD with estimated GFR <20 ml/min/1.73 m2 (2012 CKD-EPI equation)
- CKD with extracorporeal or peritoneal ultrafiltration due to diuretic-resistant fluid overload
- active tumor disease
- inflammatory or autoimmune disease requiring systemic immunosuppressive treatment
- clinically apparent infections
- recipients of solid-organ transplants
Show all 9Show fewer
- anticipated life expectancy of <12 months
- likelihood of receiving advanced therapy (mechanical circulatory assist device/cardiac transplant)
- pregnancy or possibility of pregnancy in the next 12 months
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Clinic Giessen and Marburg - Campus Giessen
Giessen, Hesse, 35392
About this study
Official title: Urinary Dickkopf-3 for Prognosis and Monitoring of Glomerular Filtration Rate Decline in Patients With Heart Failure
The individual course of chronic kidney disease (CKD) may vary, and improved methods for identifying which patients will experience estimated glomerular filtration rate (eGFR) decline are needed. Recently, urinary dickkopf-3 (DKK3) has been proposed to predict eGFR decline in patients with CKD, independent of presence of albuminuria. The investigators sought to examine the association between changes in DKK3 levels and eGFR decline in patients with heart failure (HF).
Read the detailed description
The individual course of chronic kidney disease (CKD) may vary, and improved methods for identifying which patients will experience estimated glomerular filtration rate (eGFR) decline are needed. Recently, urinary dickkopf-3 (DKK3) has been identified as an stress-induced, renal tubular epithelia-derived, secreted glycoprotein that induces tubulointerstitial fibrosis. Urinary DKK3 has been found to predict eGFR decline in patients with CKD, independent of presence of albuminuria, but its association with eGFR decline in patients with heart failure (HF) is unknown. The investigators sought to examine the association between changes in DKK3 and eGFR decline in patients with HF.
- Conditions
- Heart Failure, Chronic Kidney Diseases
- Being tested
- No intervention
- Medical subject headings
- Heart Failure, Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionDiagnostic test
No intervention
| Study group | Role | What they receive |
|---|---|---|
| HF | Diagnosed heart failure as described by recent guidelines. Inclusion criteria will be applied: i) minimum one symptom typical of HF: positive physical examination (e.g., bilateral oedema, increased jugular pressure) or positive clinical history (e.g., orthopnoea, history of coronary vascular disease, history of arterial hypertension, exposition to cardiotoxic drug/radiation, diuretic use); b-type natriuretic peptide (BNP) or N-terminal pro-BNP levels ≥35 or ≥125 pg/ml, respectively; and iii) classification as New York Heart Association (NYHA) functional class 2 or 3. There is no prespecified inclusion criterion with respect to left ventricular ejection fraction as congestive symptoms and prevalence of kidney dysfunction are comparable in patients with HF across the left ventricular ejection fraction spectrum. Receives: Diagnostic Test: No intervention | |
| Diabetes mellitus/hypertension | Diagnosed diabetes mellitus, with/without treatment Receives: Diagnostic Test: No intervention | |
| Hypertension | Diagnosed hypertension, with/without treatment Receives: Diagnostic Test: No intervention | |
| Cystic kidney diseases | Diagnosed cystic kidney diseases, with/without treatment Receives: Diagnostic Test: No intervention | |
| Tubulointerstitial diseases | Diagnosed tubulointerstitial diseases, with/without treatment Receives: Diagnostic Test: No intervention | |
| Glomerular diseases | Diagnosed glomerular diseases, with/without treatment Receives: Diagnostic Test: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Association between DKK3 and eGFR decline
DKK3 and eGFR (CKD-Epidemiology Collaboration equation)
Measured: 24 months
Secondary outcomes (5)
Association between proteinuria and DKK3
DKK3 and proteinuria, albuminuria, and alpha 1 microglobulin excretion
Measured: 24 months
Persistent or worsening of HF
Cardiovascular death, hospital admission for decompensated HF, or clinical HF decompensation without hospital admission (but requiring parenteral HF therapy or changes in oral HF medications including diuretics)
Measured: 24 months
Need for renal replacement therapy
Requirement of incident renal replacement therapy
Measured: 24 months
Association of venous congestion/volume overload with DKK3
B-type natriuretic peptide, clinical examination, bioimpedance analysis, echocardiography
Measured: 24 months
Association of right and left ventricular function with DKK3
Echocardiography
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2019
- Study start14 Oct 2019
- Primary completion21 Jan 2023
- Study completion6 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 290 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Giessen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Werner Seeger, MD, Study chair, University Hospital Giessen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04111094
- Sponsor's protocol ID
- AZ 122/19
- Status last verified
- May 2024
- First submitted
- 27 Sep 2019
- Last updated
- 9 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Zewinger S, Rauen T, Rudnicki M, Federico G, Wagner M, Triem S, Schunk SJ, Petrakis I, Schmit D, Wagenpfeil S, Heine GH, Mayer G, Floege J, Fliser D, Grone HJ, Speer T. Dickkopf-3 (DKK3) in Urine Identifies Patients with Short-Term Risk of eGFR Loss. J Am Soc Nephrol. 2018 Nov;29(11):2722-2733. doi: 10.1681/ASN.2018040405. Epub 2018 Oct 2.
PubMed 30279273Federico G, Meister M, Mathow D, Heine GH, Moldenhauer G, Popovic ZV, Nordstrom V, Kopp-Schneider A, Hielscher T, Nelson PJ, Schaefer F, Porubsky S, Fliser D, Arnold B, Grone HJ. Tubular Dickkopf-3 promotes the development of renal atrophy and fibrosis. JCI Insight. 2016 Jan 21;1(1):e84916. doi: 10.1172/jci.insight.84916.
PubMed 27699213
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Urinary Dickkopf-3 for Prognosis and Monitoring of Glomerular Filtration Rate Decline in Patients With Heart Failure
- ClinicalTrials.gov ID
- NCT04111094
- Acronym / sponsor ID
- AZ 122/19
- Conditions
- Heart Failure, Chronic Kidney Diseases
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 290 participants (actual)
- Lead sponsor
- University of GiessenUniversity, hospital or other
- Study start
- 14 Oct 2019 (actual)
- Primary completion
- 21 Jan 2023 (actual)
- Study completion
- 6 May 2024 (actual)
- First posted
- 1 Oct 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.
The individual course of chronic kidney disease (CKD) may vary, and improved methods for identifying which patients will experience estimated glomerular filtration rate (eGFR) decline are needed. Recently, urinary dickkopf-3 (DKK3) has been proposed to predict eGFR decline in patients with CKD, independent of presence of albuminuria. The investigators sought to examine the association between changes in DKK3 levels and eGFR decline in patients with heart failure (HF).
Detailed description
The individual course of chronic kidney disease (CKD) may vary, and improved methods for identifying which patients will experience estimated glomerular filtration rate (eGFR) decline are needed. Recently, urinary dickkopf-3 (DKK3) has been identified as an stress-induced, renal tubular epithelia-derived, secreted glycoprotein that induces tubulointerstitial fibrosis. Urinary DKK3 has been found to predict eGFR decline in patients with CKD, independent of presence of albuminuria, but its association with eGFR decline in patients with heart failure (HF) is unknown. The investigators sought to examine the association between changes in DKK3 and eGFR decline in patients with HF.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| HF | – | Diagnostic Test: No interventionDiagnosed heart failure as described by recent guidelines. Inclusion criteria will be applied: i) minimum one symptom typical of HF: positive physical examination (e.g., bilateral oedema, increased jugular pressure) or positive clinical history (e.g., orthopnoea, history of coronary vascular disease, history of arterial hypertension, exposition to cardiotoxic drug/radiation, diuretic use); b-type natriuretic peptide (BNP) or N-terminal pro-BNP levels ≥35 or ≥125 pg/ml, respectively; and iii) classification as New York Heart Association (NYHA) functional class 2 or 3. There is no prespecified inclusion criterion with respect to left ventricular ejection fraction as congestive symptoms and prevalence of kidney dysfunction are comparable in patients with HF across the left ventricular ejection fraction spectrum. |
| Diabetes mellitus/hypertension | – | Diagnostic Test: No interventionDiagnosed diabetes mellitus, with/without treatment |
| Hypertension | – | Diagnostic Test: No interventionDiagnosed hypertension, with/without treatment |
| Cystic kidney diseases | – | Diagnostic Test: No interventionDiagnosed cystic kidney diseases, with/without treatment |
| Tubulointerstitial diseases | – | Diagnostic Test: No interventionDiagnosed tubulointerstitial diseases, with/without treatment |
| Glomerular diseases | – | Diagnostic Test: No interventionDiagnosed glomerular diseases, with/without treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Outpatients ≥18 years of age with diagnosed HF or diabetes or hypertension or other etiologies of CKD
Key inclusion criteria (1 listed)
- Outpatients ≥18 years of age with diagnosed HF or diabetes or hypertension
Key exclusion criteria (9 listed)
- CKD with estimated GFR <20 ml/min/1.73 m2 (2012 CKD-EPI equation)
- CKD with extracorporeal or peritoneal ultrafiltration due to diuretic-resistant fluid overload
- active tumor disease
- inflammatory or autoimmune disease requiring systemic immunosuppressive treatment
- clinically apparent infections
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 |
|---|---|---|
| No interventionNo intervention | Diagnostic test | Cystic kidney diseases, Diabetes mellitus/hypertension, Glomerular diseases, HF, Hypertension, Tubulointerstitial diseases |
Primary outcome
Association between DKK3 and eGFR decline
Time frame: 24 months
DKK3 and eGFR (CKD-Epidemiology Collaboration equation)
5 secondary outcomes
Association between proteinuria and DKK3
Time frame: 24 months
Persistent or worsening of HF
Time frame: 24 months
Need for renal replacement therapy
Time frame: 24 months
Association of venous congestion/volume overload with DKK3
Time frame: 24 months
Association of right and left ventricular function with DKK3
Time frame: 24 months
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 9 May 2024.
- Background: PubMed 30279273Zewinger S, Rauen T, Rudnicki M, Federico G, Wagner M, Triem S, Schunk SJ, Petrakis I, Schmit D, Wagenpfeil S, Heine GH, Mayer G, Floege J, Fliser D, Grone HJ, Speer T. Dickkopf-3 (DKK3) in Urine Identifies Patients with Short-Term Risk of eGFR Loss. J Am Soc Nephrol. 2018 Nov;29(11):2722-2733. doi: 10.1681/ASN.2018040405. Epub 2018 Oct 2.
- Background: PubMed 27699213Federico G, Meister M, Mathow D, Heine GH, Moldenhauer G, Popovic ZV, Nordstrom V, Kopp-Schneider A, Hielscher T, Nelson PJ, Schaefer F, Porubsky S, Fliser D, Arnold B, Grone HJ. Tubular Dickkopf-3 promotes the development of renal atrophy and fibrosis. JCI Insight. 2016 Jan 21;1(1):e84916. doi: 10.1172/jci.insight.84916.
- Individual participant dataSharing planned: Undecided
Related trials for Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
Recruiting
Evaluation of a French Hospital Discharge Therapeutic Education Program by Nurses for Heart Failure Patient (EduSor)
Heart Failure
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruiting
RELIEVE-HFrEF TRIAL: REducing Lung congestIon Symptoms Using the v-wavE Shunt in adVancEd Heart Failure With Reduced EF
Heart Failure and Reduced Ejection Fraction, Heart Failure Chronic
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.
Werner Seeger, MD study chair
University Hospital Giessen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Heart Failure and Chronic Kidney Diseases, run by University of Giessen at 1 site in Germany.
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 1 inclusion and 9 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 9 May 2024. 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 Germany. 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.
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?
Association between DKK3 and eGFR decline (time frame: 24 months). 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 NCT04111094, which also lists 2 linked publications.
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 May 2024.