Chronic Kidney DiseasesPhase 4PROMISENCT06256991
Potassium Correction for RAAS Optimization in Chronic Kidney Disease
A Phase 4 study testing Patiromer 8400 MG [Veltassa] in people with Chronic Kidney Diseases and Hyperkalemia, run by University Medical Center Groningen at 1 site in Netherlands.
Trial summary
The goal of this placebo-controlled, double-blinded cross-over trial is to test whether patiromer, compared with placebo, better enables up-titration of RAAS-blocker treatment in patients with chronic kidney disease stage 3b/4. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Kidney Diseases, Hyperkalemia, Hypertension
- What is being tested?
- Patiromer 8400 MG [Veltassa]
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Apr 2024to Dec 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
- Age ≥ 18 years;
- CKD stage 3b-4 (eGFR 15-44 mL/min/1.73 m2)
- Albumin-creatinine ratio >3 mg/mmol, or proteinuria >0.05g/24u, or protein-creatinine ratio > 5mg/mmol
- Systolic blood pressure >130 mmHg or use of one or more antihypertensive drugs;
- Serum K+ 4.0-5.0 mmol/L;
- On sub-maximal dose ACEi/ARB
Who cannot join
- prior ACEi/ARB dose reduction due to a drop in eGFR by >25% in the last year;
- history of severe hyperkalaemia (>6.0 mmol/L) in the last year;
- pregnancy or breastfeeding
- life expectancy <12 months
- the use of lithium, potassium-sparing diuretics, potassium supplements, trimethoprim or NSAIDS
- kidney transplant recipients, or diagnosis of autosomal dominant polycystic kidney disease or other non-glomerular kidney disease
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
University Medical Center Groningen
Groningen
Martin de Borst, prof. dr.
About this study
Official title: Potassium Correction for Renin-angiotensin-aldosterone System Optimization in Chronic Kidney Disease
The goal of this placebo-controlled, double-blinded cross-over trial is to test whether patiromer, compared with placebo, better enables up-titration of RAAS-blocker treatment in patients with chronic kidney disease stage 3b/4.
The main questions it aims to answer are:
Read more
- Does patiromer allow uptitration of irbesartan, resulting in a significant reduction in albuminuria and blood pressure?
- Does patiromer allow uptitration of irbesartan, resulting in a significant reduction in blood pressure?
The trial contains the following interventions:
- Participants will be switched from their ACEi/ARB to a standardised dose of irbesartan (150 mg/d).
- During two 12-week study periods, participants will receive either patiromer 8.4 g/d or placebo. The order of study periods is randomized.
- At the start of each study period irbesartan will be up-titrated to 300 mg/d.
- After 1 and 6 weeks, at both periods, plasma potassium will be measured and the irbesartan dose will be reduced to 150 mg/d in case plasma potassium exceeds 5.0 mmol/L.
- At 12 weeks from the start of the study period, the endpoints will be assessed.
- Between the two study periods, there is a 6-week washout. Irbesartan dose during the wash-out period will be 150mg/d. After washout, participants will switch from the patiromer arm to the placebo arm or vice versa.
Read the detailed description
The PROMISE trial is a randomized, double-blind, placebo controlled cross-over trial where individuals are participating for 36 weeks. The trial consists of a 6-week run-in period, followed by two 12-week study periods, separated by a 6-week washout period.
First, during a run-in period, each participant will be converted from their ACEi/ARB dose to irbesartan 150 mg once daily. Individuals who already used irbesartan 150mg once daily before trial participation will remain on this dose during the run-in period. After six weeks, blood and 24-hour urine samples will be collected (baseline visit) and participants will be randomized to patiromer or placebo (start of study period A). The participant, research team, and treating physician will be blinded to treatment allocation (patiromer or placebo), while irbesartan will remain open-label.
At one week after start of study period A and B, participants will perform a home blood pressure measurement and visit a local lab to verify the plasma potassium level (safety visit), in combination with a scheduled phone consultation. The following actions may be taken: 1) If plasma potassium is >5.0 mmol/L or eGFR is >25% lower than baseline, the dose of irbesartan will be reduced to 150 mg/d and remain so during the remainder of the study period; 2) If systolic blood pressure is <110 mmHg, the participant has symptoms of hypotension, and plasma potassium is <5.0 mmol/L, antihypertensive co-medication may be adjusted, if applicable. If there is no antihypertensive co-medication that can be adjusted, the irbesartan dose will be reduced to 150 mg/d during the remainder of the study period.
At six weeks after start of the study period, there will be an in-hospital study visit. Blood samples will be collected, and office blood pressure will be measured. Any of the same two actions as described above may be taken in case of hyperkalaemia, severe acute kidney function decline or hypotension, respectively.
At the end of each 12-week study period, blood and 24-hour urine samples will be collected, and home (as well as office) blood pressure will be measured to establish the study endpoints. In addition, the study medication (patiromer/placebo) will be stopped and irbesartan dose will be reduced (or maintained) at 150 mg once daily. After a 6-week washout period, the second baseline will take place (measurements identical to the first baseline), which marks the start of study period B. During study period B, participants who had been randomized to patiromer in period A will now receive placebo and vice versa. The measurements during study period B will be identical to period A. At 12 weeks after the start of study period B, the protocol is completed and patients will return to their original medication.
The investigators chose a cross-over study design to be able to use participants as their own control; this will enhance statistical power and reduce the number of required participants. Based on previous studies, it is known that 6 weeks are sufficient to reach stable albuminuria and blood pressure after an ARB dose change. Therefore, even if halfway the 12-week study period a dose reduction is made, there is enough time for albuminuria and blood pressure to stabilize before the end of the study period (i.e., when the primary endpoint is established). A 6-week washout period is inserted to avoid carry-over effects.
- Conditions
- Chronic Kidney Diseases, Hyperkalemia, Hypertension
- Being tested
- Patiromer 8400 MG [Veltassa], Placebo
- Medical subject headings
- Renal Insufficiency, Chronic, Hyperkalemia, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Patiromer 8400 MG [Veltassa]Drug
Patiromer is a cation-exchanging polymer intended for oral intake that is not resorbed from the gastro-intestinal tract. Patiromer has been approved by the European Medicines Agency (EMA) and is available for clinical use in The Netherlands for the indication of hyperkalemia in adults. It contains calcium-sorbitol complex as a counter-ion. Patiromer increases the faecal excretion of potassium in the gastro-intestinal lumen by exchange with part of the calcium. This results in a lower concentration of free potassium in the gastro-intestinal lumen, reducing in turn plasma potassium concentration. After initiation of patiromer, a clinically significant reduction in plasma potassium can be observed at around 7 hours, the effect persists for approximately 24 hours. Patiromer is excreted by the fecal route, 24-48 hrs after ingestion. Since patiromer is not absorbed or metabolized by the body, other drugs are not expected to influence the efficacy of patiromer.
PlaceboDrug
Placebo is a powder with a similar appearance, smell, and taste as patiromer, but without and clinically detectable effects. It is intended for oral intake.
| Study group | Role | What they receive |
|---|---|---|
| Patiromer | Experimental | All participants will receive patiromer 8.4g/d (powder for oral suspension) during one of the two 12-week study periods. Following a 6-week washout, participants will switch from the patiromer arm to the placebo arm or vice versa (cross-over design). Receives: Drug: Patiromer 8400 MG [Veltassa] |
| Placebo | Placebo comparator | All participants will receive placebo 8.4g/d (powder for oral suspension) during one of the two 12-week study periods. Following a 6-week washout, participants will switch from the patiromer arm to the placebo arm or vice versa (cross-over design). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Albumin-creatinine ratio (ACR)
The primary study endpoint is the difference in ACR in 24-hour urine at the end of each study visit, compared to the ACR at the start of the study period. This is a continuous variable that will be presented quantitatively. In case of non-normal distribution, this parameter will be log-transformed. The primary hypothesis test will be the difference between placebo and treatment groups after 2 periods.
Measured: At the end of both 12-week study periods (patiromer and placebo)
Secondary outcomes (5)
Blood pressure
Systolic and diastolic blood pressure, assessed by a 24-hour ambulatory blood pressure measurement at the end of each study period (continuous data)
Measured: At the end of both 12-week study periods (patiromer and placebo)
Plasma potassium
Plasma potassium level at the end of each study period (continuous data)
Measured: At the end of both 12-week study periods (patiromer and placebo)
Kidney function
Kidney function, as reflected by the estimated glomerular filtration rate (eGFR) using the combined cystatin C-creatinine-based CKD-EPI formula, at the end of each study period (continuous data)
Measured: At the end of both 12-week study periods (patiromer and placebo)
Irbesartan dose
Irbesartan dose at the end of each study period (continuous data)
Measured: At the end of both 12-week study periods (patiromer and placebo)
Adverse events
Numbers of AE/SAE during each study period (count data)
Measured: At the end of both 12-week study periods (patiromer and placebo)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2024
- Study start1 Apr 2024
- Primary completionDec 2026 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney DiseasesStudies 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
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Amsterdam University Medical Center, Frisius Medisch Centrum, Isala, Vifor Pharma, Inc., Dutch Kidney Foundation, Health Holland
- Responsible party
- Sponsor
- Investigators
- Liffert Vogt, prof. dr., Principal investigator, Amsterdam University Medical CentreAaltje Adema, dr., Principal investigator, Frisius Medisch CentrumFemke Waanders, dr., Principal investigator, Isala ZwolleMartin de Borst, prof. dr., Study chair, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06256991
- Sponsor's protocol ID
- 17237
- Acronym
- PROMISE
- Status last verified
- Dec 2025
- First submitted
- 5 Feb 2024
- Last updated
- 19 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Participants will be asked for permission to use collected personal information and biological samples for further research. Study data will be stored for 25 years in accordance with national guidelines.
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Potassium Correction for Renin-angiotensin-aldosterone System Optimization in Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT06256991
- Acronym / sponsor ID
- PROMISE / 17237
- Conditions
- Chronic Kidney Diseases, Hyperkalemia, Hypertension
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Amsterdam University Medical Center, Frisius Medisch Centrum, Isala, Vifor Pharma, Inc., Dutch Kidney Foundation, Health Holland
- Study start
- 1 Apr 2024 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 13 Feb 2024 (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 goal of this placebo-controlled, double-blinded cross-over trial is to test whether patiromer, compared with placebo, better enables up-titration of RAAS-blocker treatment in patients with chronic kidney disease stage 3b/4.
The main questions it aims to answer are:
- Does patiromer allow uptitration of irbesartan, resulting in a significant reduction in albuminuria and blood pressure?
- Does patiromer allow uptitration of irbesartan, resulting in a significant reduction in blood pressure?
The trial contains the following interventions:
- Participants will be switched from their ACEi/ARB to a standardised dose of irbesartan (150 mg/d).
- During two 12-week study periods, participants will receive either patiromer 8.4 g/d or placebo. The order of study periods is randomized.
- At the start of each study period irbesartan will be up-titrated to 300 mg/d.
- After 1 and 6 weeks, at both periods, plasma potassium will be measured and the irbesartan dose will be reduced to 150 mg/d in case plasma potassium exceeds 5.0 mmol/L.
- At 12 weeks from the start of the study period, the endpoints will be assessed.
- Between the two study periods, there is a 6-week washout. Irbesartan dose during the wash-out period will be 150mg/d. After washout, participants will switch from the patiromer arm to the placebo arm or vice versa.
Detailed description
The PROMISE trial is a randomized, double-blind, placebo controlled cross-over trial where individuals are participating for 36 weeks. The trial consists of a 6-week run-in period, followed by two 12-week study periods, separated by a 6-week washout period.
First, during a run-in period, each participant will be converted from their ACEi/ARB dose to irbesartan 150 mg once daily. Individuals who already used irbesartan 150mg once daily before trial participation will remain on this dose during the run-in period. After six weeks, blood and 24-hour urine samples will be collected (baseline visit) and participants will be randomized to patiromer or placebo (start of study period A). The participant, research team, and treating physician will be blinded to treatment allocation (patiromer or placebo), while irbesartan will remain open-label.
At one week after start of study period A and B, participants will perform a home blood pressure measurement and visit a local lab to verify the plasma potassium level (safety visit), in combination with a scheduled phone consultation. The following actions may be taken: 1) If plasma potassium is >5.0 mmol/L or eGFR is >25% lower than baseline, the dose of irbesartan will be reduced to 150 mg/d and remain so during the remainder of the study period; 2) If systolic blood pressure is <110 mmHg, the participant has symptoms of hypotension, and plasma potassium is <5.0 mmol/L, antihypertensive co-medication may be adjusted, if applicable. If there is no antihypertensive co-medication that can be adjusted, the irbesartan dose will be reduced to 150 mg/d during the remainder of the study period.
At six weeks after start of the study period, there will be an in-hospital study visit. Blood samples will be collected, and office blood pressure will be measured. Any of the same two actions as described above may be taken in case of hyperkalaemia, severe acute kidney function decline or hypotension, respectively.
At the end of each 12-week study period, blood and 24-hour urine samples will be collected, and home (as well as office) blood pressure will be measured to establish the study endpoints. In addition, the study medication (patiromer/placebo) will be stopped and irbesartan dose will be reduced (or maintained) at 150 mg once daily. After a 6-week washout period, the second baseline will take place (measurements identical to the first baseline), which marks the start of study period B. During study period B, participants who had been randomized to patiromer in period A will now receive placebo and vice versa. The measurements during study period B will be identical to period A. At 12 weeks after the start of study period B, the protocol is completed and patients will return to their original medication.
The investigators chose a cross-over study design to be able to use participants as their own control; this will enhance statistical power and reduce the number of required participants. Based on previous studies, it is known that 6 weeks are sufficient to reach stable albuminuria and blood pressure after an ARB dose change. Therefore, even if halfway the 12-week study period a dose reduction is made, there is enough time for albuminuria and blood pressure to stabilize before the end of the study period (i.e., when the primary endpoint is established). A 6-week washout period is inserted to avoid carry-over effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patiromer | Experimental | Drug: Patiromer 8400 MG [Veltassa]All participants will receive patiromer 8.4g/d (powder for oral suspension) during one of the two 12-week study periods. Following a 6-week washout, participants will switch from the patiromer arm to the placebo arm or vice versa (cross-over design). |
| Placebo | Placebo comparator | Drug: PlaceboAll participants will receive placebo 8.4g/d (powder for oral suspension) during one of the two 12-week study periods. Following a 6-week washout, participants will switch from the patiromer arm to the placebo arm or vice versa (cross-over design). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥ 18 years;
- CKD stage 3b-4 (eGFR 15-44 mL/min/1.73 m2)
- Albumin-creatinine ratio >3 mg/mmol, or proteinuria >0.05g/24u, or protein-creatinine ratio > 5mg/mmol
- Systolic blood pressure >130 mmHg or use of one or more antihypertensive drugs;
- Serum K+ 4.0-5.0 mmol/L;
Key exclusion criteria (6 listed)
- prior ACEi/ARB dose reduction due to a drop in eGFR by >25% in the last year;
- history of severe hyperkalaemia (>6.0 mmol/L) in the last year;
- pregnancy or breastfeeding
- life expectancy <12 months
- the use of lithium, potassium-sparing diuretics, potassium supplements, trimethoprim or NSAIDS
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 |
|---|---|---|
| Patiromer 8400 MG [Veltassa]Patiromer is a cation-exchanging polymer intended for oral intake that is not resorbed from the gastro-intestinal tract. Patiromer has been approved by the European Medicines Agency (EMA) and is available for clinical use in The Netherlands for the indication of hyperkalemia in adults. It contains calcium-sorbitol complex as a counter-ion. Patiromer increases the faecal excretion of potassium in the gastro-intestinal lumen by exchange with part of the calcium. This results in a lower concentration of free potassium in the gastro-intestinal lumen, reducing in turn plasma potassium concentration. After initiation of patiromer, a clinically significant reduction in plasma potassium can be observed at around 7 hours, the effect persists for approximately 24 hours. Patiromer is excreted by the fecal route, 24-48 hrs after ingestion. Since patiromer is not absorbed or metabolized by the body, other drugs are not expected to influence the efficacy of patiromer. | Drug | Patiromer |
| PlaceboPlacebo is a powder with a similar appearance, smell, and taste as patiromer, but without and clinically detectable effects. It is intended for oral intake. | Drug | Placebo |
Primary outcome
Albumin-creatinine ratio (ACR)
Time frame: At the end of both 12-week study periods (patiromer and placebo)
The primary study endpoint is the difference in ACR in 24-hour urine at the end of each study visit, compared to the ACR at the start of the study period. This is a continuous variable that will be presented quantitatively. In case of non-normal distribution, this parameter will be log-transformed. The primary hypothesis test will be the difference between placebo and treatment groups after 2 periods.
5 secondary outcomes
Blood pressure
Time frame: At the end of both 12-week study periods (patiromer and placebo)
Plasma potassium
Time frame: At the end of both 12-week study periods (patiromer and placebo)
Kidney function
Time frame: At the end of both 12-week study periods (patiromer and placebo)
Irbesartan dose
Time frame: At the end of both 12-week study periods (patiromer and placebo)
Adverse events
Time frame: At the end of both 12-week study periods (patiromer and placebo)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2025.
- Individual participant dataSharing planned: Undecided. Participants will be asked for permission to use collected personal information and biological samples for further research. Study data will be stored for 25 years in accordance with national guidelines.
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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.
Liffert Vogt, prof. dr. principal investigator
Amsterdam University Medical Centre
Aaltje Adema, dr. principal investigator
Frisius Medisch Centrum
Femke Waanders, dr. principal investigator
Isala Zwolle
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 Patiromer 8400 MG [Veltassa] in people with Chronic Kidney Diseases and Hyperkalemia, run by University Medical Center Groningen at 1 site in Netherlands.
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 6 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 19 Dec 2025. 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 Netherlands. 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 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Martin de Borst, prof. dr. (+31503616161, m.h.de.borst@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Albumin-creatinine ratio (ACR) (time frame: At the end of both 12-week study periods (patiromer and placebo)). 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 19 Dec 2025.