Safety and Benefit Study of Droxidopa to Treat Patients With Intradialytic Hypotension
Condition: Intradialytic Hypotension
MeSH terms: Hypotension
Intervention: Droxidopa; Placebo
Intervention description: Capsules containing 200 mg droxidopa; Capsules with mannitol substituted for droxidopa
Intervention MeSH terms: Droxidopa
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 85.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female and aged 18 years or over;

          2. Clinical diagnosis of ESRD;

          3. Demonstrated requirement to undergo maintenance HD 3 times per week for sessions at
             least 3 hours in duration;

          4. Medical history consistent with IDH existing for at least 1 month;

          5. Observed symptomatic intradialytic hypotension in 3 of 6 HD sessions during screening,
             as defined by as a decrease in systolic blood pressure by ≥20 mm Hg or a decrease in
             MAP by 10 mm Hg associated with symptoms that include: abdominal discomfort; yawning;
             sighing; nausea; vomiting; muscle cramps; restlessness; dizziness or fainting; and
             anxiety (definition according to: National Kidney Foundation 2007) ;

          6. Provide written informed consent to participate in the study and understand that they
             may withdraw their consent at any time without prejudice to their future medical care.

        Exclusion Criteria:

          1. Currently taking ephedrine or midodrine;

               -  Patients taking ephedrine or midodrine may enroll after a minimum 7 day washout
                  period

          2. Taking anti-hypertensive medication on the day of dialysis;

          3. Currently taking selective norepinephrine re-uptake inhibitors;

          4. Current known or suspected drug or substance abuse;

          5. Women of childbearing potential who are not using a medically accepted contraception;

             Subject Restrictions:

               -  Reproductive potential: Female subjects should be either post-menopausal
                  (amenorrhea for at least 12 consecutive months), surgically sterile, or women of
                  child-bearing potential (WOCP) who are using or agree to use acceptable methods
                  of contraception. Acceptable contraceptives include intrauterine devices (IUDs),
                  hormonal contraceptives (oral, depot, patch or injectable) and double barrier
                  methods such as condoms or diaphragms with spermicidal gel or foam.

               -  For WOCP a urine/serum beta HCG pregnancy test must be conducted at screening and
                  study termination, and a urine/serum pregnancy test must be conducted at
                  baseline; the results must be negative at screening and at baseline. WOCP must be
                  advised to use acceptable contraceptives throughout the study period and for 30
                  days after the last dose of investigational product. If hormonal contraceptives
                  are used they should be taken according to the package insert. WOCP who are not
                  currently sexually active must agree to use acceptable contraception, as defined
                  above, if they decide to become sexually active during the period of the study
                  and for 30 days after the last dose of investigational product.

          6. Sexually active males whose partner is a WOCP must agree to use condoms for the
             duration of the study and for 30 days after the last dose;

          7. Women who are pregnant or breast feeding;

          8. Known or suspected hypersensitivity to the study medication or any of its ingredients;

          9. Have active atrial fibrillation (within the last 6 months) or, in the investigator's
             opinion, have any other significant cardiac arrhythmia;

         10. Any other significant systemic, hepatic or cardiac illness;

         11. Have a history of closed angle glaucoma;

         12. Have a known or suspected malignancy (other than basal cell carcinoma);

         13. Patients with known gastrointestinal illness or other gastrointestinal disorder that
             may, in the investigator's opinion, affect the absorption of study drug;

         14. In the investigator's opinion, have clinically significant abnormalities on clinical
             examination or laboratory testing;

         15. In the investigator's opinion, are unable to adequately cooperate because of
             individual or family situation;

         16. In the investigator's opinion, are suffering from a mental disorder that interferes
             with the diagnosis and/or with the conduct of the study, e.g. schizophrenia, major
             depression, dementia;

         17. Are not able or willing to comply with the study requirements for the duration of the
             study;

         18. Have participated in another clinical trial with an investigational agent (including
             named patient or compassionate use protocol) within 30 days before the start of the
             study;

         19. Previous enrollment in the study.