Trial Outcomes & Findings for Comparison of Oral or Intravenous Thiazides vs Tolvaptan in Diuretic Resistant Decompensated Heart Failure (NCT NCT02606253)

Last Updated: 2019-11-08

Results Overview

The primary outcome will be 48-hour standing scale weight change (kg) from enrollment among the metolazone, intravenous chlorothiazide, and tolvaptan arms, using metolazone group as the comparator group for all other groups.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

60 participants

Primary outcome timeframe

48 hours

Results posted on

2019-11-08

Participant Flow

Participant milestones

Participant milestones
Measure	Metolazone Metolazone 5mg tablet orally twice daily for 48 hours. Metolazone: Metolazone (Zaroxolyn) is an oral thiazide diuretic that works in the distal convoluted tubule of the nephron to cause diuresis.	Chlorothiazide Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours Chlorothiazide: Chlorothiazide (Diuril) is an intravenous thiazide diuretic that works in the distal convoluted tubule of the nephron to cause diuresis.	Tolvaptan Tolvaptan 30mg tablet orally once daily for 48 hours tolvaptan: Tolvaptan (Samsca) is a vasopressin 2 receptor antagonist that works in the collecting duct of the nephron to cause diuresis.
Overall Study STARTED	20	20	20
Overall Study COMPLETED	15	18	20
Overall Study NOT COMPLETED	5	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Metolazone Metolazone 5mg tablet orally twice daily for 48 hours. Metolazone: Metolazone (Zaroxolyn) is an oral thiazide diuretic that works in the distal convoluted tubule of the nephron to cause diuresis.	Chlorothiazide Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours Chlorothiazide: Chlorothiazide (Diuril) is an intravenous thiazide diuretic that works in the distal convoluted tubule of the nephron to cause diuresis.
Overall Study Adverse Event	2	0
Overall Study Protocol Violation	2	1
Overall Study Physician Decision	1	1

Baseline Characteristics

Comparison of Oral or Intravenous Thiazides vs Tolvaptan in Diuretic Resistant Decompensated Heart Failure

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours	Total n=60 Participants Total of all reporting groups
Age, Continuous	61 years STANDARD_DEVIATION 15 • n=5 Participants	67 years STANDARD_DEVIATION 11 • n=7 Participants	58 years STANDARD_DEVIATION 14 • n=5 Participants	62 years STANDARD_DEVIATION 14 • n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	17 Participants n=4 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	16 Participants n=7 Participants	12 Participants n=5 Participants	43 Participants n=4 Participants
Race/Ethnicity, Customized White	13 Participants n=5 Participants	12 Participants n=7 Participants	15 Participants n=5 Participants	40 Participants n=4 Participants
Race/Ethnicity, Customized Black	6 Participants n=5 Participants	8 Participants n=7 Participants	5 Participants n=5 Participants	19 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	20 participants n=5 Participants	20 participants n=7 Participants	20 participants n=5 Participants	60 participants n=4 Participants
Number of Patients with HF reduced Ejection fraction	12 Participants n=5 Participants	16 Participants n=7 Participants	18 Participants n=5 Participants	46 Participants n=4 Participants
Number of Patients with HF preserved Ejection fraction	8 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	14 Participants n=4 Participants
Ischemic cardiomyopathy	6 Participants n=5 Participants	9 Participants n=7 Participants	8 Participants n=5 Participants	23 Participants n=4 Participants
Mean Left ventricular ejection fraction (%)	35 % STANDARD_DEVIATION 19 • n=5 Participants	29 % STANDARD_DEVIATION 17 • n=7 Participants	27 % STANDARD_DEVIATION 13 • n=5 Participants	30 % STANDARD_DEVIATION 16 • n=4 Participants
Number of patients with coronary artery disease	10 Participants n=5 Participants	12 Participants n=7 Participants	13 Participants n=5 Participants	35 Participants n=4 Participants
Number of patients with hypertension	18 Participants n=5 Participants	18 Participants n=7 Participants	13 Participants n=5 Participants	49 Participants n=4 Participants
Number of patients with diabetes mellitus	12 Participants n=5 Participants	19 Participants n=7 Participants	11 Participants n=5 Participants	42 Participants n=4 Participants
Number of patients with chronic kidney disease	16 Participants n=5 Participants	16 Participants n=7 Participants	12 Participants n=5 Participants	44 Participants n=4 Participants
Number of patients with atrial fibrillation	13 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	32 Participants n=4 Participants
Cumulative IV Loop diuretic dose in Furosemide Equivalents for previous 24 hours (mg/24 hrs)	680 mg/24 hours STANDARD_DEVIATION 517 • n=5 Participants	611 mg/24 hours STANDARD_DEVIATION 464 • n=7 Participants	546 mg/24 hours STANDARD_DEVIATION 324 • n=5 Participants	612 mg/24 hours STANDARD_DEVIATION 429 • n=4 Participants
Total urine output in past 12 hours (mls)	1170 ml STANDARD_DEVIATION 412 • n=5 Participants	1372 ml STANDARD_DEVIATION 500 • n=7 Participants	1022 ml STANDARD_DEVIATION 465 • n=5 Participants	1118 ml STANDARD_DEVIATION 476 • n=4 Participants
Diuretic Efficiency	199 ml urine output/ 40mg IV furosemide STANDARD_DEVIATION 129 • n=5 Participants	254 ml urine output/ 40mg IV furosemide STANDARD_DEVIATION 161 • n=7 Participants	174 ml urine output/ 40mg IV furosemide STANDARD_DEVIATION 96 • n=5 Participants	209 ml urine output/ 40mg IV furosemide STANDARD_DEVIATION 134 • n=4 Participants
Serum sodium (mEq/L)	139 mEq/L STANDARD_DEVIATION 2 • n=5 Participants	138 mEq/L STANDARD_DEVIATION 4 • n=7 Participants	137 mEq/L STANDARD_DEVIATION 3 • n=5 Participants	138 mEq/L STANDARD_DEVIATION 3 • n=4 Participants
Serum potassium (mEq/L)	3.9 mEq/L STANDARD_DEVIATION 0.5 • n=5 Participants	4.0 mEq/L STANDARD_DEVIATION 0.4 • n=7 Participants	4.0 mEq/L STANDARD_DEVIATION 0.5 • n=5 Participants	3.9 mEq/L STANDARD_DEVIATION 0.5 • n=4 Participants
Serum chloride (mEq/L)	100 mEq/L STANDARD_DEVIATION 6 • n=5 Participants	100 mEq/L STANDARD_DEVIATION 4 • n=7 Participants	100 mEq/L STANDARD_DEVIATION 5 • n=5 Participants	100 mEq/L STANDARD_DEVIATION 5 • n=4 Participants
BUN (mg/dl)	46 mg/dl STANDARD_DEVIATION 19 • n=5 Participants	48 mg/dl STANDARD_DEVIATION 31 • n=7 Participants	41 mg/dl STANDARD_DEVIATION 23 • n=5 Participants	45 mg/dl STANDARD_DEVIATION 25 • n=4 Participants
Serum Creatinine (mg/dl)	2.0 mg/dl STANDARD_DEVIATION 0.9 • n=5 Participants	2.1 mg/dl STANDARD_DEVIATION 0.7 • n=7 Participants	1.8 mg/dl STANDARD_DEVIATION 0.7 • n=5 Participants	1.9 mg/dl STANDARD_DEVIATION 0.7 • n=4 Participants
Glomerular filtration rate (ml/min/m2)	41 ml/min/m2 STANDARD_DEVIATION 19 • n=5 Participants	36 ml/min/m2 STANDARD_DEVIATION 15 • n=7 Participants	46 ml/min/m2 STANDARD_DEVIATION 24 • n=5 Participants	41 ml/min/m2 STANDARD_DEVIATION 20 • n=4 Participants
Systolic blood pressure (mmHg)	114 mmHg STANDARD_DEVIATION 13 • n=5 Participants	119 mmHg STANDARD_DEVIATION 20 • n=7 Participants	114 mmHg STANDARD_DEVIATION 12 • n=5 Participants	115 mmHg STANDARD_DEVIATION 15 • n=4 Participants
Patient-Reported Visual Analog Congestion Score from 0 cm (worst symptoms) to 10cm (best)	2.5 cm on dyspnea analog scale STANDARD_DEVIATION 2.2 • n=5 Participants	4.1 cm on dyspnea analog scale STANDARD_DEVIATION 2.2 • n=7 Participants	3.8 cm on dyspnea analog scale STANDARD_DEVIATION 2.3 • n=5 Participants	3.4 cm on dyspnea analog scale STANDARD_DEVIATION 2.3 • n=4 Participants
Number of patients on Beta blocker therapy	16 Participants n=5 Participants	13 Participants n=7 Participants	17 Participants n=5 Participants	46 Participants n=4 Participants
Number of patients on ACEI/ARB/ARNI therapy	6 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants	21 Participants n=4 Participants
Number of patients on Aldosterone antagonist therapy	10 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants	27 Participants n=4 Participants
Number of patients on Intravenous Inotrope therapy	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants
Number of patients on Loop diuretic infusion 100mg bolus & 20mg/h	10 Participants n=5 Participants	10 Participants n=7 Participants	9 Participants n=5 Participants	29 Participants n=4 Participants
Number of patients on Loop diuretic infusion 100mg bolus & 30mg/h	10 Participants n=5 Participants	10 Participants n=7 Participants	11 Participants n=5 Participants	31 Participants n=4 Participants

PRIMARY outcome

Timeframe: 48 hours

Population: Intention to treat analysis

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Weight Change Over 48 Hours	-4.6 kg Standard Deviation 2.7	-5.8 kg Standard Deviation 2.7	-4.1 kg Standard Deviation 3.3

SECONDARY outcome

Timeframe: 48 hours

Population: Intention to treat

Net urine output from enrollment to the end of study at 48 hours measured in liters

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Net Urine Output	-7.8 liters Interval -10.1 to -6.6	-8.8 liters Interval -10.9 to -7.4	-9.8 liters Interval -13.8 to -6.4

SECONDARY outcome

Timeframe: 48 hours

Mean change in serum creatinine (mg/dl) from enrollment to end of study at 48 hours

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Mean Change in Serum Creatinine	0.3 mg/dl Standard Deviation 0.3	0.5 mg/dl Standard Deviation 0.5	0.03 mg/dl Standard Deviation 0.3

SECONDARY outcome

Timeframe: hospital discharge an average of 5 days

Mean change in glomerular filtration rate from enrollment to end of study at hospital discharge, an average of 5 days

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Mean Change in Glomerular Filtration Rate at Discharge	-2 ml/min/m2 Standard Deviation 19	-2 ml/min/m2 Standard Deviation 13	-6 ml/min/m2 Standard Deviation 10

SECONDARY outcome

Timeframe: 48 hours

Mean change in serum potassium (mEq/L) from enrollment to end of study at 48 hours

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Mean Change in Serum Potassium	-0.1 mEq/L Standard Deviation 0.7	-0.2 mEq/L Standard Deviation 0.5	0.1 mEq/L Standard Deviation 0.5

SECONDARY outcome

Timeframe: 48 hours

Cumulative dose of potassium supplementation (mEq) administered from enrollment to end of study at 48 hours

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Potassium Supplementation	103 mEq Standard Deviation 131	63 mEq Standard Deviation 60	58 mEq Standard Deviation 56

SECONDARY outcome

Timeframe: 48 hours

Incidence of hypokalemia (serum potassium less than 3.5mEq/L ) from enrollment to end of study

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Number of Patients With Hypokalemia	3 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: 24 hours

Provider escalation of loop diuretic dosage at 24 hours for urine output less than 3 L at 24 hours

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Number of Patients With Escalation of Loop Diuretic Therapy	4 Participants	4 Participants	2 Participants

SECONDARY outcome

Timeframe: 48 hours

Incidence of new atrial or ventricular arrhythmias from enrollment to end of study at 48 hours

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Number of Patients With Cardiac Arrhythmias	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 48 hours

SBP \< 85 mmHg plus medical intervention for symptomatic hypotension

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Number of Patients With Symptomatic Hypotension	2 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: 48 hours

Change in estimated glomerular filtration rate (ml/min/m2) from baseline to 48 hours

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Change in eGFR From Baseline to 48 Hours	-6 ml/min/m2 Standard Deviation 7	-9 ml/min/m2 Standard Deviation 9	2 ml/min/m2 Standard Deviation 11

SECONDARY outcome

Timeframe: 48 hours

Mean change in serum sodium (mEq/L) from enrollment to end of study at 48 hours

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Mean Change in Serum Sodium	-1 mEq/L Standard Deviation 3	-1 mEq/L Standard Deviation 3	4 mEq/L Standard Deviation 5

OTHER_PRE_SPECIFIED outcome

Timeframe: Enrollment to hospital discharge an average of 5 days

Incidence of death from study enrollment to hospital discharge, an average of 5 days

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Number of Patients With In-hospital Mortality	0 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 48 hours

Incidence of new initiation of dopamine, dobutamine, or milrinone from enrollment to end of study at 48 hours

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Number of Patients With New Inotrope Utilization	1 Participants	0 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: enrollment to hospital discharge an average of 5 days

Incidence of Renal replacement therapy utilization (hemodialysis, ultrafiltration) from enrollment to hospital discharge, an average of 5 days

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Number of Patients With Renal Replacement Therapy Utilization	0 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 48 hours

Diuretic Efficiency is calculated as 48hr urine output/ 48hr Furosemide equivalents in milligrams

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Diuretic Efficiency	217 UOP / 40mg IV furosemide Standard Deviation 107	294 UOP / 40mg IV furosemide Standard Deviation 123	326 UOP / 40mg IV furosemide Standard Deviation 213

OTHER_PRE_SPECIFIED outcome

Timeframe: 48 hours

Change in serum chloride (mEq/L) from baseline to 48 hrs

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Change in Serum Chloride From Baseline	-7 mEq/L Standard Deviation 4	-7 mEq/L Standard Deviation 2	2 mEq/L Standard Deviation 3

OTHER_PRE_SPECIFIED outcome

Timeframe: 48 hours

Participants will score their congestion on a 10cm scale ranging from "Best" (10cm) to "Worst" (0cm). Change in score (units in centimeters) from baseline to 48 hours.

Outcome measures

Outcome measures
Measure	Metolazone n=20 Participants Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 Participants Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 Participants Tolvaptan 30mg tablet orally once daily for 48 hours
Change in Patient Congestion Score	4.0 cm of dyspena analog scale Interval 2.5 to 7.0	3.0 cm of dyspena analog scale Interval 2.0 to 4.6	3.0 cm of dyspena analog scale Interval 2.0 to 5.0

Adverse Events

Metolazone

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Chlorothiazide

Serious events: 0 serious events

Other events: 6 other events

Deaths: 1 deaths

Tolvaptan

Serious events: 0 serious events

Other events: 10 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Metolazone n=20 participants at risk Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 participants at risk Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 participants at risk Tolvaptan 30mg tablet orally once daily for 48 hours
Cardiac disorders Hypotension	10.0% 2/20 • Number of events 2 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.

Other adverse events

Other adverse events
Measure	Metolazone n=20 participants at risk Metolazone 5mg tablet orally twice daily for 48 hours.	Chlorothiazide n=20 participants at risk Chlorothiazide 500mg intravenous infusion over 30 minutes twice daily for 48 hours	Tolvaptan n=20 participants at risk Tolvaptan 30mg tablet orally once daily for 48 hours
Metabolism and nutrition disorders Increase in serum sodium	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	10.0% 2/20 • Number of events 2 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.
Cardiac disorders Non-severe hypotension	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	10.0% 2/20 • Number of events 2 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.
Musculoskeletal and connective tissue disorders Gout flare	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	15.0% 3/20 • Number of events 3 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.
Musculoskeletal and connective tissue disorders muscle cramping	10.0% 2/20 • Number of events 2 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	10.0% 2/20 • Number of events 2 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	5.0% 1/20 • Number of events 1 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.
Renal and urinary disorders Serum creatinine increase > 1mg /dl	5.0% 1/20 • Number of events 1 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	15.0% 3/20 • Number of events 3 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.
Metabolism and nutrition disorders Severe Hypokalemia < 3.0 mEq/L	5.0% 1/20 • Number of events 1 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.
Gastrointestinal disorders Nausea/vomiting	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	5.0% 1/20 • Number of events 1 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.
Nervous system disorders Delirium	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	5.0% 1/20 • Number of events 1 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.
Musculoskeletal and connective tissue disorders Tremor	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	5.0% 1/20 • Number of events 1 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.
Cardiac disorders cardioembolic stroke	5.0% 1/20 • Number of events 1 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.	0.00% 0/20 • Adverse events were collected during the 48 hour study and over a subsequent 30 day follow up period. Events detailed below are through the 30 day follow up period.

Additional Information

Dr. Zachary Cox, Associate Professor

Lipscomb University College of Pharmacy

Phone: 6159667163

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place