Diuretic-Based Blood Pressure Treatment Compared With Usual Care for Kidney Disease

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for adults with moderate to severe chronic kidney disease whose high blood pressure is not controlled by their current treatment. It compares a diuretic-based (water pill) treatment plan with usual care.

Age

18 years and older. People over 80 need a clinical frailty score of 5 or less.

Sex

Men and women can join.

Disease stage

Moderate or advanced chronic kidney disease, with an eGFR (a measure of kidney function) of 15 to 44.9 mL/min/1.73m² using the CKD-EPI formula. High blood pressure that is not controlled.

Earlier treatment

People must take at least one ACE inhibitor (ACEi) or ARB blood pressure drug at the highest dose they can tolerate, unchanged for at least one month. Other blood pressure drugs are allowed alongside, or if ACEi or ARB are not tolerated. People taking two or more diuretics, or mineralocorticoid receptor antagonists, cannot join. People with polycystic kidney disease treated with Tolvaptan cannot join.

Biomarker or test result

Clinic blood pressure above 140 and/or 90 mmHg, confirmed by home readings above 135 and/or 85 mmHg or by daytime ambulatory blood pressure monitoring (a portable device worn during the day).

Main reasons for not taking part

• Pregnant or breastfeeding women, or women who could become pregnant without highly effective birth control.
• A heart attack, hospital stay for heart failure, or stroke in the last three months, or severe heart failure (NYHA III-IV).
• Low blood sodium (<130 mmol/L) or abnormal blood potassium (<3,5 mmol/L or >5,5 mmol/L).
• A solid organ transplant, or cancer that currently needs chemotherapy.
• Signs of low body fluid, dizziness or fainting on standing up, liver cirrhosis Child B-C, or being unable to take the diuretics used.

The registry criteria, word for word

What the trial wants to find out

Chronic kidney disease (CKD) is a major public health issue worldwide. Hypertension is the first risk factor in patients with CKD for mortality, cardiovascular disease and end-stage renal disease. It's now well established that lowering blood pressure (BP) reduces renal and cardiovascular complications in this high-risk population. In the general population, in addition to lifestyle interventions, the strategy to initiate and escalate a BP-lowering drug treatment is well described. The drug therapies recommended to achieve optimal BP control in the general population are the following: blockers of the renin-angiotensin system (angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB)), diuretics (thiazides and thiazide-like diuretics), and calcium channel blockers. For patients with CKD, the guidelines advise to start the BP-lowering agent with ACEi or ARB, but then, there is no strong evidence to support the preferential use of any particular agent in controlling BP and the results of clinical trials are discordant. In the NephroTest cohort, a French cohort of patients with CKD stage 1 to 5, among 2015 patients, 1782 had hypertension, only 54% had a diuretic and 44% had uncontrolled hypertension. In this cohort, extracellular fluid (ECF) overload was an independent determinant of hypertension, uncontrolled hypertension and apparent treatment resistant hypertension. In the same cohort, ECF overload was independently associated with end-stage kidney disease and death. Our hypothesis is that patients with CKD and uncontrolled hypertension are fluid overloaded and that the second line of treatment after an ACEi or an ARB should be a diuretic. We hypothesize that a specific algorithm to lower BP in patients with moderate to severe CKD based on diuretics will be more effective in term of cardiovascular event, mortality and evolution to end-stage kidney disease as compared to standard of care.

The 2 groups in the trial

• Experimental groupTreatment being tested

  Antihypertensive algorithm based on diuretics agents : the clinicians will adjust the drug therapy according to the antihypertensive algorithm based on diuretics agents.

  Treatment: Antihypertensive algorithm

• Control groupExisting treatment, for comparison

  Standard of care : the clinicians will adapt the antihypertensive strategy according to his own standard of care which can be pharmacological or non-pharmacological therapies.

  Treatment: Standard of care