Study: NCT04334668

Adverse event: Low output and elevated filling pressure
Serious: yes
Organ System: Cardiac disorders
Notes: Low cardiac output \& elevated filling pressures found during right heart catherization. Transferred to ICU for swan guided afterload optimization. Study drug discontinued 24 hours prior to discontinuation of IV diuretic.
Frequency: 1 affected / 34 at risk

Adverse event: Readmission for weight gain
Serious: yes
Organ System: General disorders
Notes: Readmission with weight gain and lower extremity swelling secondary to recurrent heart failure. Diuresed with lasix and discharged 4 days later.
Frequency: 1 affected / 34 at risk

Adverse event: Readmission
Serious: yes
Organ System: General disorders
Notes: Patient readmitted with high blood pressure, diffuse joint pain, and compensated heart failure. Rheumatology felt presentation was consistent with either reactive arthritis or hydralazine induced arthralgias, unrelated to the study.
Frequency: 1 affected / 34 at risk

Adverse event: ICU transfer
Serious: yes
Organ System: Respiratory, thoracic and mediastinal disorders
Notes: Patient transferred to ICU for hematemesis and underwent squamous carcinoma resection. Patient transitioned to DNRCC and died of respiratory failure in the setting of post-operative complications from bladder malignancy surgery.
Frequency: 1 affected / 34 at risk

Adverse event: Leukocytosis and worsening renal function
Serious: yes
Organ System: General disorders
Notes: Readmitted for fluid overload. Developed altered mental status related to leukocytosis \& worsening renal function. Dialysis didn't improve mental status. Made DNR/DNI \& died on day of transfer to hospice. Only 1 dose of study medication taken.
Frequency: 1 affected / 34 at risk

Adverse event: Uncontrolled dyspnea
Serious: yes
Organ System: General disorders
Notes: Readmitted with neutropenic fever related to leukemia. Admitted to hospice for uncontrolled dyspnea and died. Unrelated to study medication
Frequency: 1 affected / 34 at risk

Adverse event: ICU
Serious: yes
Organ System: General disorders
Notes: During the study a routine clinical Right Heart Catheterization was performed to assess volume status. Patient transferred to CICU due to elevated filling pressures and low output therapy. Cardiac index normalized with nitroprusside therapy.
Frequency: 1 affected / 34 at risk

Adverse event: Increase in creatinine
Serious: yes
Organ System: Renal and urinary disorders
Notes: Creatinine increased from 2.6 at End of Study visit to 3.19 eight days post study. Dialysis started and renal function improved. Unlikely to be study related
Frequency: 1 affected / 34 at risk

Adverse event: Transferred to ICU
Serious: no
Organ System: Respiratory, thoracic and mediastinal disorders
Notes: Transferred to ICU for lethargy \& hypoxia. Treated for aspiration pneumonia/pneumonitis on top of baseline pulmonary congestion. Unlikely to be related to study medication.
Frequency: 1 affected / 34 at risk

Adverse event: Hyponatraemia
Serious: no
Organ System: General disorders
Notes: 2 days after study medication finished patient developed hyponatremia. Sodium level decreased from 131 to 125.
Frequency: 1 affected / 34 at risk

Adverse event: Nausea
Serious: no
Organ System: Gastrointestinal disorders
Notes: Patient developed nausea after 1st dose of study medication
Frequency: 1 affected / 34 at risk

Adverse event: Nausea/Vomiting
Serious: no
Organ System: Gastrointestinal disorders
Notes: Patient stated they threw up the first dose of study medication and didn't take any more.
Frequency: 1 affected / 34 at risk

Adverse event: Worsening Renal Function
Serious: yes
Organ System: Renal and urinary disorders
Notes: \>48 hours after study medication completion subject had worsening Renal Function, Right Heart Catheterization showed low output. Transferred to ICU for vasodilation.
Frequency: 1 affected / 31 at risk

Adverse event: Hypokalaemia
Serious: yes
Organ System: General disorders
Notes: 35 days after receiving final study medication patient readmitted with hypokalemia \& ICD shock aborted cardiac arrest from VF. Patient had a history of ICD shocks. Incident \& hypokalemia occurred after receiving metolazone (unrelated to the study).
Frequency: 1 affected / 31 at risk

Adverse event: ICU transfer
Serious: yes
Organ System: Cardiac disorders
Notes: Underwent Right Heart Catheterization which revealed markedly elevated filling pressures and low cardiac index. Transferred to CICU. Hemodynamics improved with sodium nitroprusside.
Frequency: 1 affected / 31 at risk

Adverse event: Readmitted
Serious: yes
Organ System: General disorders
Notes: Hemoglobin dropped to 5.6, down from 8. Received 2 units of blood with appropriate subsequent rise in hemoglobin.
Frequency: 1 affected / 31 at risk

Adverse event: VF arrest
Serious: yes
Organ System: Cardiac disorders
Notes: Passed away after a VF arrest. Developed pulseless VT in the setting of un-revascularized coronary disease and severe biventricular cardiomyopathy.
Frequency: 1 affected / 31 at risk

Adverse event: COVID 19 infection
Serious: yes
Organ System: Respiratory, thoracic and mediastinal disorders
Notes: Readmission for shortness of breath. Died during admission from COVID-19 infection. Death and readmission not related to study drug.
Frequency: 1 affected / 31 at risk

Adverse event: Respiratory decompensation
Serious: yes
Organ System: General disorders
Notes: ICU transfer and subsequent death related to respiratory decompensation from aspiration \& pulmonary infection. Acute Kidney Injury and worsening respiratory function followed. Unrelated to study.
Frequency: 1 affected / 31 at risk

Adverse event: Readmission
Serious: yes
Organ System: General disorders
Notes: Readmission with worsening renal function and heart failure. Occurrence \>3weeks after study medication, unrelated to study.
Frequency: 1 affected / 31 at risk

Adverse event: ICU transfer
Serious: yes
Organ System: General disorders
Notes: Creatinine increased from 1.01 on admission to 1.98 on study day one. Transferred to ICU. Subsequent Right Heart Catheterization showed elevated biventricular filling pressures \& normal cardiac index. Unlikely to be related to study.
Frequency: 1 affected / 31 at risk

Adverse event: ICU
Serious: yes
Organ System: Cardiac disorders
Notes: Transferred to ICU 5 days post study. Pulmonary Artery catheter numbers showed Pulmonary Capillary Wedge Pressure 34 and Cardiac Index 1.96. Accepted for LVAD at a later date.
Frequency: 1 affected / 31 at risk

Adverse event: Gout Flare up
Serious: no
Organ System: General disorders
Notes: Gout flare up, likely due to diuretic use and unlikely related to study medication.
Frequency: 1 affected / 31 at risk

Adverse event: Hypokalaemia
Serious: no
Organ System: General disorders
Notes: Hypokalemia (K3.1), required holding of lasix. Hypokalemia is a common side effect of metolazone. Unable to rule out study medication as cause.
Frequency: 1 affected / 31 at risk

Adverse event: Hypokalemia, VF arrest
Serious: no
Organ System: General disorders
Notes: Hypokalemia, VF arrest, ICD shock aborted cardiac arrest. Patient history of ICD shocks. Incident and hypokalemia occurred after receiving metolazone. Can't rule out study medication as the cause.
Frequency: 1 affected / 31 at risk

Adverse event: Nausea
Serious: no
Organ System: Gastrointestinal disorders
Notes: 1 dose of study medication held due to patient nausea
Frequency: 1 affected / 31 at risk