Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06256991 |
| Other study ID # |
17237 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
April 2024 |
| Est. completion date |
December 2026 |
Study information
| Verified date |
February 2024 |
| Source |
University Medical Center Groningen |
| Contact |
Martin de Borst, prof. dr. |
| Phone |
+31503616161 |
| Email |
m.h.de.borst[@]umcg.nl |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical 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.
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.
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.
