Safety and Benefit Study of Droxidopa to Treat Patients With Intradialytic Hypotension
Condition: Intradialytic Hypotension
MeSH terms: Hypotension
Study type: Interventional
Phase: Phase 2

Summary: 
      In clinical trials in Japan, droxidopa has been shown to be effective in affecting blood
      pressure changes upon orthostatic challenge in patients with autonomic dysfunction, as well
      as reducing the severity and frequency of symptoms of orthostatic hypotension in these
      patients. The efficacy of droxidopa in ameliorating symptoms in patients undergoing dialysis
      has also been demonstrated in the literature and clinical trials conducted in Japan. The
      current study will investigate the clinical efficacy of two different doses of droxidopa in
      patients with intradialytic hypotension over a 4 week treatment period with a placebo
      control. The clinical efficacy will be evaluated by changes in hypotension- related symptoms,
      as well as changes in blood pressure prior to, during and following, HD sessions as compared
      to their pre-treatment baseline values.
    

Detailed description: 
      This is a phase II, multi-center, randomized, double-blind, placebo-controlled study to
      evaluate the efficacy and safety of droxidopa in HD patients with intradialytic hypotension.
      The study will be conducted in up to 15 centers, with a sufficient number of patients
      enrolled to allow 75 patients to be randomized into 3 study groups (25 randomized to placebo,
      25 randomized to 400 mg droxidopa, and 25 randomized to 600 mg droxidopa).

      The study will consist of an initial screening period (up to 7 days) to confirm eligibility
      followed by a 2 week baseline, and a 4 week treatment period. During baseline and treatment
      visits SBP and DBP measurements will be collected using a consistent method immediately pre-,
      during and immediately post-dialysis. SBP, DBP and heart rate measurements will be taken
      every 20 minutes during HD sessions.

      There will be 19 scheduled visits, not including the post-treatment follow-up visit, during
      this trial; Visit 1 (Screening), Visits 2 through 7 (baseline and randomization), Visits 8
      through 19 (tri-weekly treatment visits). Each visit will coincide with the patient's normal
      dialysis treatments.

      All patients will be followed for 30 days following the completion of the active treatment
      period (or premature withdrawal) to check for the occurrence of adverse events (AEs).

      Patients will attend the study center as out-patients.

      Eligible patients will be assigned a unique identification number at screening, and prior to
      the first treatment visit will be randomized to one of the following treatment groups:

      Group A: Droxidopa at 400 mg (2 capsules each containing 200 mg droxidopa plus one capsule
      with mannitol substituted for droxidopa) Group B: Droxidopa at 600 mg (3 capsules each
      containing 200 mg droxidopa) Group C: Placebo (3 capsules with mannitol substituted for
      droxidopa) Each patient will take 3 capsules 1 hour prior to each dialysis procedure with
      approximately 100 mL (typically half a glass) of water.

      The primary measure of efficacy will be the change from baseline (visits 2-7) in average mean
      arterial blood pressure compared to that during treatment (visit 14-19).

      The secondary measures of efficacy will be:

        -  Change between baseline (visits 2-7) and treatment (visits 14-19) in average mean nadir
           systolic and diastolic blood pressures during hemodialysis;

        -  Change in the number of hypotension-induced interventions during hemodialysis (HD)
           sessions;

        -  Change in hypotension-induced symptoms measured during hemodialysis;

        -  Change in daily symptoms associated with hemodialysis;

        -  Change in fatigue using the Multidimensional Fatigue Inventory (MFI-20). The safety of
           droxidopa will be evaluated based on the occurrence of treatment-emergent adverse events
           (AE) and specific evaluation of blood pressure, heart rate (HR), ECG, and laboratory
           findings across the study.
    

Intervention name(s): Droxidopa; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Capsules containing 200 mg droxidopa; Capsules with mannitol substituted for droxidopa
Intervention MeSH terms: Droxidopa
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment