Suggested Protocol Elements For Clinical Research Monitoring

To inform understanding of the potential efficacy and safety of hydroxychloroquine-azithromycin, we strongly advocate for enrollment of all patients who are candidates into IRB-approved clinical research protocols.

In balancing the importance of evaluating a therapeutic option where no effective therapies exist, while maximizing the safe use of QT prolonging medications in the research setting, we suggest protocols address the following:

  1. Pre-enrollment
    • Discontinue and avoid all other non-critical QT prolonging agents.
    • Assess baseline ECG and renal function, hepatic function, serum potassium and serum magnesium.
    • When possible, have an experienced cardiologist/electrophysiologist measure QTc, and seek pharmacist input in the setting of acute renal or hepatic failure.
    • Assess baseline risk of QT prolongation using the risk score of Tisdale et al.
  2. Enrollment
    • Establish contraindications to study enrollment due to excessive risk of drug proarrhythmia. Potential absolute or relative contraindications for hydroxychloroquine-azithromycin combination use in clinical research include:
      • Known congenital long QT syndrome
      • For inpatients:
        1. Baseline QTc >500 msec (or >530-550 msec if QRS >120 msec), or
        2. Tisdale risk ≥11 + inability to monitor with serial ECGs or telemetry
      • For outpatients:
        1. Baseline QTc >480 msec (or >510-530 msec if QRS >120 msec), or
        2. Tisdale risk ≥11
  3. Ongoing monitoring, dose adjustment and drug discontinuation
    • Monitor and optimize serum potassium and magnesium.
    • Monitor use of medications that may precipitate electrolyte shifts, such as loop and thiazide diuretics.
    • Prescribe a plan for continuous cardiac telemetry and/or interval ECGs for QTc monitoring, with provisions for well-resourced and poorly-resourced enrollment sites.
    • Discontinue therapy for observed polymorphic ventricular tachycardia or syncope with concern for arrhythmic etiology.
    • Prescribe a dose reduction strategy for patients who experience QT prolongation with therapy (QTc >500 msec with normal QRS; >530-550 msec if QRS >120 msec; or increase in QTc >30-60 msec after initiation of treatment).