Chlorthalidone in Chronic Kidney Disease
Condition: Renal Insufficiency, Chronic; Hypertension
MeSH terms: Renal Insufficiency; Renal Insufficiency, Chronic
Intervention: Chlorthalidone; Placebo
Intervention description: This is a forced-titration study and the study drug will be increased if goal BP is not achieved (dosage of chlorthalidone not to exceed 50 mg); This is a forced-titration study and placebo will be increased if goal BP is not achieved.
Intervention MeSH terms: Chlorthalidone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 160.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      It is estimated that in the United States there are approximately 8 million individuals who
      have moderate to severe chronic kidney disease (CKD). Among them hypertension is common and
      is often poorly controlled due to an expanded volume state; diuretics are frequently
      prescribed. Loop diuretics are potent and effective in lowering blood pressure (BP) but their
      use is associated with acute kidney injury. Thiazide diuretics, on the other hand, are less
      potent, their use may be associated with less acute kidney injury, but as yet there are no
      firm data to support that thiazide diuretic therapy can improve BP among subjects with
      advanced CKD. The investigators found 13 studies on the use of thiazide diuretics in advanced
      CKD either alone or in combination with loop diuretics and concluded that thiazides may be
      useful. Thiazides cause a negative Na balance, increase Na excretion by 10-15% and weight
      loss by 1-2 kg in observational studies. Observational data show that thiazides lead to an
      improvement in seated clinic BP of about 10-15 mmHg systolic and 5-10 mmHg diastolic whereas
      randomized trials show about a 15 mmHg reduction in mean BP. Randomized trials had only
      between 7 and 23 subjects each; accordingly, larger studies are needed to evaluate their
      safety and efficacy in moderate to advanced CKD.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age greater than 18 years.

          2. Calculated glomerular filtration rate (GFR) by 4-component Modification of Diet in
             Renal Disease (MDRD) formula < 30 ml/min/1.73m2 but ≥15 mL/min/1.73m2. The hospital
             laboratory uses isotope dilution mass spectrometry (IDMS) calibrated creatinine and
             the appropriate formula is used to estimate GFR.

          3. Hypertension. This is defined as BP of either ≥130 systolic or ≥80 mmHg by 24-hour
             ambulatory BP monitoring.

          4. Treatment with antihypertensive drugs: This would require the use of at least one
             antihypertensive drug. One of the drugs should be either an angiotensin converting
             enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). If these are
             contraindicated then use of a beta-blocker is required prior to randomization.

        Exclusion Criteria:

          1. Use of thiazide or thiazide-like drugs in the previous 12 weeks.

          2. Use of furosemide in a dose >200 mg/d.

          3. BP of either ≥160 systolic or ≥100 mmHg by 24-hour ambulatory BP monitoring.

          4. Expected to receive renal replacement therapy within the next 3 months.

          5. Myocardial infarction, heart failure hospitalization, or stroke ≤3 months prior to
             randomization.

          6. Pregnant or breastfeeding women or women who are planning to become pregnant or those
             not using a reliable form of contraception (oral contraceptives. condoms and
             diaphragms will be considered reliable).

          7. Known hypersensitivity to thiazide or sulfa drugs.

          8. Organ transplant recipient or therapy with immunosuppressive agents.