SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01005602

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Use of a Simplified Nomogram and Pharmacogenetics to Individualize Digoxin Dosing in Heart Failure Patients vs. Standard Care

Dosing methods for digoxin, a drug used to treat heart failure, have not been updated in decades despite evidence in recent years suggesting that blood levels of digoxin achieved with traditional dosing practices may increase the risk of adverse events. We developed a simple dosing tool that targets lower blood levels of digoxin that have been associated with improved outcomes compared to higher blood levels. The aim of this study is to determine if this simplified dosing tool is more effective than standard digoxin dosing practices at achieving lower blood levels and also to determine if digoxin dosing may be further optimized by incorporating patients' genetic information believed to influence the drug's properties.

NCT01005602 Heart Failure
MeSH: Heart Failure
HPO: Congestive heart failure Left ventricular dysfunction Right ventricular failure

2 Interventions

Name: Digoxin Dosing per Nomogram

Description: Simplified dosing nomogram for digoxin. The dose is determined by plotting a subject's creatinine clearance (x-axis) and ideal body weight (y-axis) on the nomogram. Alternatively, the dose may be determined by plotting creatinine clearance (x-axis) and gender/height (z-axis).

Type: Other

Digoxin Dosing per Nomogram

Name: Digoxin

Description: All patients included in the trial were treated with digoxin as clinically indicated. The intervention for this study required determining the digoxin dose via a proposed nomogram.

Type: Drug

Digoxin Dosing per Nomogram Standard Digoxin Dosing


Primary Outcomes

Measure: Percent of Patients Achieving a Desired Steady-state Serum Digoxin Concentration Between 0.5 - 0.9ng/ml

Time: Steady-state (2 - 4 weeks after initiation)

Secondary Outcomes

Measure: Mean Serum Digoxin Concentration

Time: Steady-state (2 - 4 weeks after initiation)

Measure: Serum Digoxin Concentration < 1.0 ng/ml

Time: Steady-state (2 - 4 weeks after initiation)

Description: 55 patients in the Digoxin Dosing per Nomogram group consented to the Pharmacogenetic substudy and provided blood samples to perform pharmacogenetic analyses. We compared serum digoxin concentrations by ABCB1 genotype.

Measure: Serum Digoxin Concentration by ABCB1 Single Nucleotide Polymorphism (SNP) C1236T

Time: Steady-state (2 - 4 weeks after initiation)

Description: Serum digoxin concentration by genotypes for the ABCB1 SNP C3435T

Measure: Serum Digoxin Concentration by ABCB1 SNP C3435T

Time: Steady-state (2 - 4 weeks after initiation)

Description: Serum digoxin concentration by ABCB1 SNP genotypes

Measure: Serum Digoxin Concentration by ABCB1 SNP G2677T/A

Time: Steady-state (2 - 4 weeks after initiation)

Purpose: Treatment

Allocation: Non-Randomized

Parallel Assignment


There are 3 SNPs

SNPs


1 C1236T

Serum Digoxin Concentration by ABCB1 Single Nucleotide Polymorphism (SNP) C1236T. --- C1236T ---


2 C3435T

We compared serum digoxin concentrations by ABCB1 genotype.. Serum Digoxin Concentration by ABCB1 SNP C3435T. --- C3435T ---

Serum digoxin concentration by genotypes for the ABCB1 SNP C3435T. --- C3435T ---


3 G2677T

Serum Digoxin Concentration by ABCB1 SNP G2677T/A. --- G2677T ---



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