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Report for Clinical Trial NCT02606253

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Comparison of Oral Thiazides vs Intravenous Thiazides vs Tolvaptan in Combination With Loop Diuretics for Diuretic Resistant Decompensated Heart Failure

Broad Objectives: To determine the comparative efficacy of commonly employed strategies to overcome loop diuretic resistance when added to concomitant loop diuretics in hospitalized decompensated heart failure patients with hypervolemia Specific Aims: 1. Compare the 48-hour weight change of either intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in decompensated heart failure 2. Compare the adverse effects of electrolyte depletion and renal function changes between intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in acute heart failure 3. Pharmacoeconomic analysis of the direct costs of intravenous chlorothiazide or oral tolvaptan compared to standard-of-care oral metolazone when combined with standardized loop diuretic dosing for diuretic resistance in acute heart failure The investigators will conduct a dual center, randomized, double-blind, double-dummy, parallel design trial comparing: oral metolazone, intravenous chlorothiazide, or oral tolvaptan, in combination with loop diuretics in 60 patients hospitalized for hypervolemic decompensated heart failure and displaying loop diuretic resistance.

NCT02606253 Heart Failure
MeSH: Heart Failure
HPO: Congestive heart failure Left ventricular dysfunction Right ventricular failure

3 Interventions

Name: tolvaptan

Description: Tolvaptan (Samsca) is a vasopressin 2 receptor antagonist that works in the collecting duct of the nephron to cause diuresis.

Type: Drug

Tolvaptan

Name: Chlorothiazide

Description: Chlorothiazide (Diuril) is an intravenous thiazide diuretic that works in the distal convoluted tubule of the nephron to cause diuresis.

Type: Drug

Chlorothiazide

Name: Metolazone

Description: Metolazone (Zaroxolyn) is an oral thiazide diuretic that works in the distal convoluted tubule of the nephron to cause diuresis.

Type: Drug

Metolazone


Primary Outcomes

Description: 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.

Measure: Weight Change Over 48 Hours

Time: 48 hours

Secondary Outcomes

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

Measure: Net Urine Output

Time: 48 hours

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

Measure: Mean Change in Serum Creatinine

Time: 48 hours

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

Measure: Mean Change in Glomerular Filtration Rate at Discharge

Time: hospital discharge an average of 5 days

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

Measure: Mean Change in Serum Potassium

Time: 48 hours

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

Measure: Potassium Supplementation

Time: 48 hours

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

Measure: Number of Patients With Hypokalemia

Time: 48 hours

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

Measure: Number of Patients With Escalation of Loop Diuretic Therapy

Time: 24 hours

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

Measure: Number of Patients With Cardiac Arrhythmias

Time: 48 hours

Description: SBP < 85 mmHg plus medical intervention for symptomatic hypotension

Measure: Number of Patients With Symptomatic Hypotension

Time: 48 hours

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

Measure: Change in eGFR From Baseline to 48 Hours

Time: 48 hours

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

Measure: Mean Change in Serum Sodium

Time: 48 hours

Other Outcomes

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

Measure: Number of Patients With In-hospital Mortality

Time: Enrollment to hospital discharge an average of 5 days

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

Measure: Number of Patients With New Inotrope Utilization

Time: 48 hours

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

Measure: Number of Patients With Renal Replacement Therapy Utilization

Time: enrollment to hospital discharge an average of 5 days

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

Measure: Diuretic Efficiency

Time: 48 hours

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

Measure: Change in Serum Chloride From Baseline

Time: 48 hours

Description: 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.

Measure: Change in Patient Congestion Score

Time: 48 hours

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 Q12H

Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H ---

Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H --- --- Q12H ---

Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H --- --- Q12H --- --- Q12H ---

Patients will be randomized to either intravenous chlorothiazide 500mg IV Q12H + an oral placebo capsule Q12H or intravenous placebo infusion Q12H + a capsule containing either oral metolazone 5mg PO Q12H or oral tolvaptan 30mg once daily and placebo capsule in the evening dose. --- Q12H --- --- Q12H --- --- Q12H --- --- Q12H ---



HPO Nodes


HPO:
Congestive heart failure
Genes 250
PTEN HJV BAZ1B PEX7 HBA1 ND1 TNNT2 TRIM37 ACAD9 AGPAT2 TRNS1 LMNA EYA4 ND4 MYH7 LMNA RFC2 DSP NDUFAF3 TMEM43 SF3B1 HADHB SLC25A11 COX2 ENG HBA2 CEP19 LMNA TRNQ TRNQ GTF2IRD1 IDS MYL3 MYH7 ATXN7 ND6 HNRNPA1 CACNA1S FLNC XYLT2 EPG5 BSCL2 MYH6 FBN1 TRNK GBA SLC2A10 TRNV COX3 RET PRKAR1A MDH2 TRNK IRF5 MYH7 GPR35 TRNL1 ENG SURF1 STAT1 NSMCE2 SGCD ATP5F1A PLN TUBB PLOD1 CAV3 SLC25A26 SLC19A2 MYD88 GLA TPM1 GNPTAB RBM20 LMNA CDH23 TRNW CLIP2 MYPN TSC1 BMP2 HAMP TRNF ADCY5 LMNA LDB3 TTN ELN ENPP1 CAVIN1 TF MAX ELAC2 NDUFS2 CYTB DES DMD MYLK2 MAX TBL2 HLA-DRB1 ALMS1 PNPLA2 SLC17A5 COG7 SLC22A5 MYH7 PSMB8 SCN1B EYA4 MST1 FH TMEM127 MYH7 ND6 PPARG SDHA MAPRE2 COX1 JUP PSEN2 RASA1 ND5 SLC25A3 LMNA DLST TRNF IFIH1 ADCY5 SDHB SCN4A FXN GDF2 GTF2I HADHA GJA1 GNA11 RYR1 HFE SNAP29 TRNH TNNI3K FLNA TRNS2 SDHAF2 LMNA ACVRL1 TSC2 CASR FOS FGFR3 TRNK TRNL1 BCHE CCR6 CAV1 FGF23 VHL TMEM70 ADAMTSL2 DTNA PRKAG2 BAG3 TRNE SMAD4 TRNS2 ACAD9 SDHC PRKAR1A TAZ CAV1 ALMS1 TRNS1 NDUFB8 LIMK1 CLIC2 GATAD1 SDHD NDUFAF1 PRDM16 SELENON TRPM4 ACTC1 PRKAR1A SCN5A RPS19 TRIP4 FBLN5 SDHB NDUFB11 ATP6V1A HNRNPA2B1 CCN2 PSMB8 PPA2 TRNL1 COX1 RAB3GAP2 TNNI3 HFE COL1A2 TRNC CLIC2 DSP ND1 SCO2 JUP SDHD TRNW COX3 EFEMP2 AGGF1 TMEM127 TCF4 LMNA DSP KIF1B COL1A1 COX2 TPI1 GNPTAB FGD1 PSEN1 RET GLB1 KCNJ5 PHYH DES GTPBP3 HADHB WRN ND5 MECP2 HADHA GDNF VCL GLA TTN KIF1B VHL VCP ABCC6 PPARG CP XYLT1 TET2 DNAJC19 IKBKG NKX2-5 ABCC6
Left ventricular dysfunction
Genes 67
TRNL1 SDHAF1 LDLRAP1 LDLR FBN1 RYR2 APOB POMT1 MAT2A FKRP LMNA TOP3A TRNW ABCG8 TRNC ND1 TRNS2 MYH7 LDB3 TRNS1 TTN POLG2 EYA4 POMT2 FOXE3 SMAD4 TGFBR2 SGCG PPCS DYSF TRNK CYTB TRDN SMAD3 MYH11 POLG ACTA2 COX2 SLC25A4 SDHD TGFB3 PRKG1 MYLK TWNK TRNQ SDHB POMT2 LAMA2 RRM2B ND6 MYH11 TGFB2 ND5 ELN COX1 MFAP5 PRDM16 TRNV SDHA COX3 MYH11 TRNF LOX PCSK9 CASQ2 TGFBR1 ABCG5
Right ventricular failure
Genes 7
DAXX SDHD TTN BMPR2 MYH7 SELENON ATRX