Trial Outcomes & Findings for Pharmacogenetic Prediction of Metoprolol Effectiveness (NCT NCT02293096)

NCT ID: NCT02293096

Last Updated: 2021-09-16

Results Overview

Participants with at least a 10% decrease in SBP

Recruitment status

TERMINATED

Study phase

Target enrollment

462 participants

Primary outcome timeframe

4-6 weeks status post initiation

Results posted on

2021-09-16

Participant Flow

322 participants screen failed or withdrew after consent, but prior to starting the study \& receiving the intervention

Participant milestones

Participant milestones
Measure	Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping The parent study will integrate covariates to predict metoprolol effectiveness for SBP decline of 10%. All patients will receive metoprolol. The following covariates will be used to predict metoprolol effectiveness: clinical variables (Age, sex, race/ethnicity, co-medications, and BMI) CYP2D6 genotype, CYP2D6 phenotype, and metabolomic factors. metoprolol succinate Genotyping: CYP2D6 only clinically pertinent pathway of metoprolol metabolism and polymorphisms have been associated with altered levels of metoprolol. ADRB1 is the drug target and polymorphism in this receptor has been associated with variable drug response. Genotyping will occur after the treatment phase is complete. CYP2D6 Phenotyping: Phenotype can be discordant from what is predicted by genotype. CYP2D6 henotyping using dextromethorphan will be used. Investigators will be blind to the patient blood pressure outcome for this intervention.
Overall Study STARTED	140
Overall Study COMPLETED	140
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacogenetic Prediction of Metoprolol Effectiveness

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping n=140 Participants The parent study will integrate covariates to predict metoprolol effectiveness for SBP decline of 10%. All patients will receive metoprolol. The following covariates will be used to predict metoprolol effectiveness: clinical variables (Age, sex, race/ethnicity, co-medications, and BMI) CYP2D6 genotype, CYP2D6 phenotype, and metabolomic factors. metoprolol succinate Genotyping: CYP2D6 only clinically pertinent pathway of metoprolol metabolism and polymorphisms have been associated with altered levels of metoprolol. ADRB1 is the drug target and polymorphism in this receptor has been associated with variable drug response. Genotyping will occur after the treatment phase is complete. CYP2D6 Phenotyping: Phenotype can be discordant from what is predicted by genotype. CYP2D6 henotyping using dextromethorphan will be used. Investigators will be blind to the patient blood pressure outcome for this intervention.
Age, Continuous	52.12 years STANDARD_DEVIATION 11.05 • n=5 Participants
Sex: Female, Male Female	55 Participants n=5 Participants
Sex: Female, Male Male	85 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	116 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	60 Participants n=5 Participants
Race (NIH/OMB) White	70 Participants n=5 Participants
Race (NIH/OMB) More than one race	6 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	140 participants n=5 Participants

PRIMARY outcome

Timeframe: 4-6 weeks status post initiation

Participants with at least a 10% decrease in SBP

Outcome measures

Outcome measures
Measure	Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping n=140 Participants The parent study will integrate covariates to predict metoprolol effectiveness for SBP decline of 10%. All patients will receive metoprolol. The following covariates will be used to predict metoprolol effectiveness: clinical variables (Age, sex, race/ethnicity, co-medications, and BMI) CYP2D6 genotype, CYP2D6 phenotype, and metabolomic factors. metoprolol succinate Genotyping: CYP2D6 only clinically pertinent pathway of metoprolol metabolism and polymorphisms have been associated with altered levels of metoprolol. ADRB1 is the drug target and polymorphism in this receptor has been associated with variable drug response. Genotyping will occur after the treatment phase is complete. CYP2D6 Phenotyping: Phenotype can be discordant from what is predicted by genotype. CYP2D6 henotyping using dextromethorphan will be used. Investigators will be blind to the patient blood pressure outcome for this intervention.
Blood Pressure Decline	85 Participants

SECONDARY outcome

Timeframe: 4-6 weeks

10 % decline from pre-initiation heart rate will considered a HR decline success. Number of of participants with at least 10% decline is reported.

Outcome measures

Outcome measures
Measure	Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping n=140 Participants The parent study will integrate covariates to predict metoprolol effectiveness for SBP decline of 10%. All patients will receive metoprolol. The following covariates will be used to predict metoprolol effectiveness: clinical variables (Age, sex, race/ethnicity, co-medications, and BMI) CYP2D6 genotype, CYP2D6 phenotype, and metabolomic factors. metoprolol succinate Genotyping: CYP2D6 only clinically pertinent pathway of metoprolol metabolism and polymorphisms have been associated with altered levels of metoprolol. ADRB1 is the drug target and polymorphism in this receptor has been associated with variable drug response. Genotyping will occur after the treatment phase is complete. CYP2D6 Phenotyping: Phenotype can be discordant from what is predicted by genotype. CYP2D6 henotyping using dextromethorphan will be used. Investigators will be blind to the patient blood pressure outcome for this intervention.
Heart Rate Decline	67 Participants

SECONDARY outcome

Timeframe: 6 weeks

Occurrence of adverse drug events will be captured and stratified by CYP2D6 metabolizer status (Poor Metabolizer (PM), Extensive Metabolizer (EM), Intermediate Metabolizer (IM), and Ultra rapid Metabolizer).

Outcome measures

Outcome measures
Measure	Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping n=140 Participants The parent study will integrate covariates to predict metoprolol effectiveness for SBP decline of 10%. All patients will receive metoprolol. The following covariates will be used to predict metoprolol effectiveness: clinical variables (Age, sex, race/ethnicity, co-medications, and BMI) CYP2D6 genotype, CYP2D6 phenotype, and metabolomic factors. metoprolol succinate Genotyping: CYP2D6 only clinically pertinent pathway of metoprolol metabolism and polymorphisms have been associated with altered levels of metoprolol. ADRB1 is the drug target and polymorphism in this receptor has been associated with variable drug response. Genotyping will occur after the treatment phase is complete. CYP2D6 Phenotyping: Phenotype can be discordant from what is predicted by genotype. CYP2D6 henotyping using dextromethorphan will be used. Investigators will be blind to the patient blood pressure outcome for this intervention.
Adverse Drug Events: CYP2D6 Metabolizer Status CYP2D6 metabolizer status: EM	3 participants with events
Adverse Drug Events: CYP2D6 Metabolizer Status Other Metabolizer Statuses	0 participants with events

SECONDARY outcome

Timeframe: 6 weeks

Occurrence of adverse drug events will be captured and stratified by ADRB1 genotype (strong responder, good responder, non-responder).

Outcome measures

Outcome measures
Measure	Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping n=140 Participants The parent study will integrate covariates to predict metoprolol effectiveness for SBP decline of 10%. All patients will receive metoprolol. The following covariates will be used to predict metoprolol effectiveness: clinical variables (Age, sex, race/ethnicity, co-medications, and BMI) CYP2D6 genotype, CYP2D6 phenotype, and metabolomic factors. metoprolol succinate Genotyping: CYP2D6 only clinically pertinent pathway of metoprolol metabolism and polymorphisms have been associated with altered levels of metoprolol. ADRB1 is the drug target and polymorphism in this receptor has been associated with variable drug response. Genotyping will occur after the treatment phase is complete. CYP2D6 Phenotyping: Phenotype can be discordant from what is predicted by genotype. CYP2D6 henotyping using dextromethorphan will be used. Investigators will be blind to the patient blood pressure outcome for this intervention.
Adverse Drug Events: ADRB1 Genotype ADRB1 genotype: Strong Responder	1 participants with events
Adverse Drug Events: ADRB1 Genotype ADRB1 genotype: Good Responder	2 participants with events
Adverse Drug Events: ADRB1 Genotype ADRB1 genotype: Non-responder	0 participants with events

OTHER_PRE_SPECIFIED outcome

Timeframe: 0-6 weeks

The top 5 metabolomic factors associated with SBP decline will be captured and stratified by CYP2D6 genotype and phenotype groups.

Outcome measures

Outcome data not reported

Adverse Events

Metoprolol Succinate, Genotyping, Clinical Factors, and Phenotyping

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Andrew Monte, MD, PhD

University of Colorado Denver | Anschutz

Phone: 3037241111

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place