SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02606253

Developed by Shray Alag, 2019.
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

Time: 48 hours

Secondary Outcomes

Description: Net urine output from enrollment to the end of study at 48 hours measured in milliliters and collected either by a foley catheter or via a urine collection cup.

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 serum creatinine (mg/dl) from enrollment to end of study at hospital discharge, an average of 5 days

Measure: Mean Change in Serum Creatinine 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 severe hypokalemia (serum potassium less than 3.0mEq/L ) from enrollment to end of study

Measure: Severe Hypokalemia

Time: 48 hours

Description: Provider escalation of loop diuretic dosage at 24 hours

Measure: 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: Cardiac Arrhythmias

Time: 48 hours

Description: pharmacoeconomic analysis of the direct costs in U.S. dollars in each arm for the cost of: study medication. All medication and therapy costs will be defined as the Redbook average wholesale price at the time of the trial to reduce inter-institutional price differences and improve external validity of the analysis.

Measure: Pharmacoeconomic analysis: study drugs

Time: 48 hours

Description: pharmacoeconomic analysis of the direct costs in U.S. dollars in each arm for the cost of additional non-trial protocol laboratory analysis cost related to monitoring of electrolytes

Measure: Pharmacoeconomic analysis: laboratory monitoring

Time: 48 hours

Description: pharmacoeconomic analysis of the direct costs in U.S. dollars in each arm for the cost of addition of additional therapies for suboptimal diuresis (inotropic therapy, vasodilators)

Measure: Pharmacoeconomic analysis: additional therapies

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: In-hospital mortality

Time: Enrollment to hospital discharge an average of 5 days

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

Measure: 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: 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: Incidence of hypotension (defined as a systolic blood pressure less than 85mmHg for 2 repeated measurements within 30 minutes or lasting at least 30 minutes or symptomatic hypotension necessitating clinical intervention) from enrollment to 48 hours end of study

Measure: Hypotension

Time: 48 hours

Description: Participants will score their congestion on a 10 point scale ranging from "Best" to "Worst"

Measure: Patient Congestion score

Time: at enrollment, at 24 hours, and at 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 180
HJV TPM1 VHL HFE MYD88 ATP6V1A CACNA1S NDUFB11 FLNA SCO2 TCF4 FLNC MYH6 PNPLA2 MYH7 FBLN5 EYA4 MYL3 PSEN1 PSEN2 RASA1 CLIP2 DSP GPR35 DNAJC19 COG7 SGCD DTNA ENPP1 ACAD9 FOS HLA-DRB1 MAX GNPTAB KIF1B EFEMP2 NDUFAF3 BAG3 AGPAT2 WRN TUBB SLC19A2 PSMB8 IKBKG GBA AGGF1 ACTC1 BAZ1B PEX7 CDH23 CP CASR IRF5 RPS19 TSC1 TSC2 TMEM43 SLC25A26 CAV1 FXN RET PPARG ACVRL1 RFC2 IDS MDH2 PTEN GTF2IRD1 NSMCE2 GDF2 TMEM127 SELENON TTN HNRNPA1 NDUFB8 TF MECP2 TRIP4 HNRNPA2B1 ADCY5 ABCC6 ELAC2 RBM20 NDUFS2 STAT1 RYR1 EPG5 SNAP29 SLC25A3 MST1 SLC2A10 SLC17A5 IFIH1 GJA1 DES FGF23 TNNI3K JUP LIMK1 PHYH LDB3 FBN1 GTF2I GLA NDUFAF1 TRNC GLB1 LMNA COX1 ALMS1 COX2 COX3 SDHAF2 CYTB CLIC2 ATXN7 KCNJ5 SURF1 RAB3GAP2 ND1 MYPN TMEM70 SLC22A5 SCN4A ND4 PPA2 ND5 ND6 FGD1 PRKAR1A GATAD1 TRNE TRNF GNA11 CCN2 CCR6 CAVIN1 BSCL2 TRNH FGFR3 ELN HADHA TRNK TRNL1 HADHB HAMP DMD TRNQ PRKAG2 TRNS1 FH HBA1 TRNS2 GTPBP3 HBA2 TRNV TNNI3 TRNW TNNT2 ENG MAPRE2 PLN PLOD1 PRDM16 TRIM37 TBL2 ATP5F1A SDHA TAZ SDHB VCL ADAMTSL2 SDHC VCP SDHD CEP19 SMAD4 COL1A1 COL1A2 TPI1
Left ventricular dysfunction
Genes 62
POMT2 TGFB2 TGFB3 TGFBR1 LDLRAP1 TGFBR2 SDHAF1 MFAP5 MYH7 LDB3 MYH11 EYA4 FBN1 MYLK TRNC LMNA COX1 COX2 COX3 SLC25A4 CYTB FKRP SGCG LOX MAT2A RRM2B POLG ND1 ACTA2 ND5 ND6 LAMA2 TWNK CASQ2 TRNF APOB ELN TRNK TRNL1 PRKG1 POMT1 TRNQ TRNS1 TRNS2 POLG2 TRNV TRNW PPCS PRDM16 TRDN TTN LDLR ABCG5 ABCG8 TOP3A SDHA RYR2 SDHB SMAD3 SDHD PCSK9 FOXE3
Right ventricular failure
Genes 7
DAXX MYH7 ATRX BMPR2 SELENON SDHD TTN