Trial Outcomes & Findings for Genotype-supported Versus Conventional Proton Pump Inhibitor Dosing (NCT NCT02930824)

Last Updated: 2024-05-16

Results Overview

The RDQ was developed to monitor treatment response over time and evaluates 6 symptoms (12 items) covering 3 domains: heartburn, regurgitation, and upper abdominal pain. Each symptom is evaluated using a 6-point Likert scale to assess frequency and severity over the previous week. Each symptom is rated from 1 (did not have) to 6 (severe), and the RDQ mean score is calculated as the mean response to the 12 items. The RDQ mean score thus ranges from 1 to 6 and has been psycho-metrically validated.

Recruitment status

COMPLETED

Study phase

Target enrollment

185 participants

Primary outcome timeframe

Change from baseline and 12 weeks

Results posted on

2024-05-16

Participant Flow

Participant milestones

Participant milestones
Measure	Adult Genotype Guided Treatment For adults randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. CYP2C19 genotyping: All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.	Adult Conventional Treatment For adults randomized to the genotype-supported arm no genotype will be provided to physicians to assist in dosing.	Pediatric Genotype Guided Treatment For children randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. CYP2C19 genotyping: All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.	Pediatric Conventional Treatment For children randomized to the genotype-supported arm no genotype will be provided to physicians to assist in dosing.
Overall Study STARTED	62	63	30	30
Overall Study COMPLETED	56	57	20	23
Overall Study NOT COMPLETED	6	6	10	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Genotype-supported Versus Conventional Proton Pump Inhibitor Dosing

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adult Genotype Guided Treatment n=62 Participants For adults randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. CYP2C19 genotyping: All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.	Adult Conventional Treatment n=63 Participants For adults randomized to the conventional arm no genotype will be provided to physicians to assist in dosing.	Pediatric Genotype Guided Treatment n=30 Participants For children randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. CYP2C19 genotyping: All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.	Pediatric Conventional Treatment n=30 Participants For children randomized to the conventional arm no genotype will be provided to physicians to assist in dosing.	Total n=185 Participants Total of all reporting groups
Age, Continuous	53.8 years STANDARD_DEVIATION 15.7 • n=5 Participants	50.5 years STANDARD_DEVIATION 16.3 • n=7 Participants	12 years STANDARD_DEVIATION 3.7 • n=5 Participants	12.5 years STANDARD_DEVIATION 3.6 • n=4 Participants	39.4 years STANDARD_DEVIATION 23.1 • n=21 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	43 Participants n=7 Participants	17 Participants n=5 Participants	17 Participants n=4 Participants	120 Participants n=21 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	20 Participants n=7 Participants	13 Participants n=5 Participants	13 Participants n=4 Participants	65 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	6 Participants n=4 Participants	25 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=5 Participants	55 Participants n=7 Participants	22 Participants n=5 Participants	24 Participants n=4 Participants	149 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=5 Participants	4 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	11 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Black or African American	12 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	23 Participants n=21 Participants
Race (NIH/OMB) White	46 Participants n=5 Participants	51 Participants n=7 Participants	20 Participants n=5 Participants	27 Participants n=4 Participants	144 Participants n=21 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	2 Participants n=4 Participants	15 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	62 participants n=5 Participants	63 participants n=7 Participants	30 participants n=5 Participants	30 participants n=4 Participants	185 participants n=21 Participants

PRIMARY outcome

Timeframe: Change from baseline and 12 weeks

Population: Adult patients enrolled that have a CYP2C19 Rapid or Ultra-rapid metabolizer result.

Outcome measures

Outcome measures
Measure	Adult Genotype Guided Treatment n=17 Participants For adults randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. CYP2C19 genotyping: All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.	Adult Conventional Treatment n=18 Participants For adults randomized to the genotype-supported arm no genotype will be provided to physicians to assist in dosing.	Pediatric Genotype Guided Treatment For children randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. CYP2C19 genotyping: All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.	Pediatric Conventional Treatment For children randomized to the genotype-supported arm no genotype will be provided to physicians to assist in dosing.
Reflux Disease Questionnaire (RDQ)	-0.387 score on a scale Standard Deviation 1.2	-0.296 score on a scale Standard Deviation 0.58	—	—

PRIMARY outcome

Timeframe: Week 4 (or next available results)

Population: Children aged 5-17 years old with gastric-acid-related conditions and a completed SN-5 questionnaire at week 4 (or next available results)

The Pediatric Sinonasal Symptom Survey (SN-5) is a validated 5-item scale with each item rated on a scale of worsening symptoms from 1 (none of the time) through 7 (all of the time). Items were averaged to yield a single total score ranging from 1 (better outcomes) to 7 (worse outcomes). The total SN-5 scores were compared between the conventional and genotype-guided dosing groups to determine if one group reported worsening symptoms over the other.

Outcome measures

Outcome measures
Measure	Adult Genotype Guided Treatment For adults randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. CYP2C19 genotyping: All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.	Adult Conventional Treatment For adults randomized to the genotype-supported arm no genotype will be provided to physicians to assist in dosing.	Pediatric Genotype Guided Treatment n=16 Participants For children randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. CYP2C19 genotyping: All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.	Pediatric Conventional Treatment n=18 Participants For children randomized to the genotype-supported arm no genotype will be provided to physicians to assist in dosing.
Pediatric Sinonasal Symptom Survey (SN-5)	—	—	1.8 score on a scale Interval 1.0 to 2.3	2.6 score on a scale Interval 2.0 to 3.4

PRIMARY outcome

Timeframe: Over the 12-week period or last date of follow-up

Population: Children aged 5-17 years old with gastric-acid-related conditions with completed SafetyQ assessment over the 12-week period or last date of follow-up

Occurrence of adverse events over the 12 weeks was captured by the Safety Questionnaire (SafetyQ), which was to be completed on a weekly basis by the parents. The Safety Questionnaire (SafetyQ) asked about the presence of seven different respiratory symptoms since their last visit; upper respiratory infection, sore throat, strep throat, bronchitis, pneumonia, ear infection, and acute sinusitis. If a symptom was selected as being present since the last visit, the date of onset and patient-reported explanation of the symptom was recorded. The number of participants who reported infections were compared between each group.

Outcome measures

Outcome measures
Measure	Adult Genotype Guided Treatment For adults randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. CYP2C19 genotyping: All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.	Adult Conventional Treatment For adults randomized to the genotype-supported arm no genotype will be provided to physicians to assist in dosing.	Pediatric Genotype Guided Treatment n=26 Participants For children randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. CYP2C19 genotyping: All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.	Pediatric Conventional Treatment n=27 Participants For children randomized to the genotype-supported arm no genotype will be provided to physicians to assist in dosing.
Safety Questionnaire (SafetyQ)	—	—	20 % of participants reporting infections	44 % of participants reporting infections

PRIMARY outcome

Timeframe: Change in score from baseline to the week 4 ± 1-week

Population: Children aged 5-17 years old with gastric-acid-related conditions and a completed Gasp-Q questionnaire at baseline and week 4 ± 1-week

Gastroesophageal reflux disease (GERD) Assessment of Symptoms in Pediatrics Questionnaire (Gasp-Q) is a validated patient-reported outcome questionnaire that evaluated proton pump inhibitor therapy efficacy. Gasp-Q inquired about the severity and frequency of belly pain, chest pain, difficulty swallowing, choking, burping, nausea, pain after eating, night pain, and vomiting. If the symptom was present, the patient was asked to score the severity of the symptom ranging from 1 (Not at all severe) to 7 (Most severe). A composite score was then calculated based on the scoring of the 9 symptoms and ranged from 9 to 63.

Outcome measures

Outcome measures
Measure	Adult Genotype Guided Treatment For adults randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. CYP2C19 genotyping: All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.	Adult Conventional Treatment For adults randomized to the genotype-supported arm no genotype will be provided to physicians to assist in dosing.	Pediatric Genotype Guided Treatment n=18 Participants For children randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. CYP2C19 genotyping: All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.	Pediatric Conventional Treatment n=22 Participants For children randomized to the genotype-supported arm no genotype will be provided to physicians to assist in dosing.
Gastroesophageal Reflux Disease (GERD) Assessment of Symptoms in Pediatrics Questionnaire (Gasp-Q)	—	—	-24.0 median (IQR) composite score Interval -32.0 to -9.0	-26.0 median (IQR) composite score Interval -35.0 to 10.0

PRIMARY outcome

Timeframe: Change in score from baseline to the week 4 ± 1-week

Population: Children aged 5-17 years old with gastric-acid-related conditions with a completed PedsQL questionnaire at baseline and week 4 ± 1-week

Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Module is a validated patient-reported outcome questionnaire and Likert response scale, to evaluate proton pump inhibitor therapy efficacy. The gastrointestinal problems included in the PedsQL were stomach pain and hurt, stomach upset, food and drink limits, trouble swallowing, heartburn and reflux, gas and bloating, constipation, diarrhea, and worry. Participants were asked to rate the symptoms from 0 (never a problem) to 4 (almost always a problem).

Outcome measures

Outcome measures
Measure	Adult Genotype Guided Treatment For adults randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. CYP2C19 genotyping: All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.	Adult Conventional Treatment For adults randomized to the genotype-supported arm no genotype will be provided to physicians to assist in dosing.	Pediatric Genotype Guided Treatment n=19 Participants For children randomized to the genotype-supported arm a CYP2C19 genotype will be provided to physicians to assist in dosing. CYP2C19 genotyping: All proton pump inhibitors are metabolized in part by the CYP2C19 enzyme, which is encoded by the highly polymorphic CYP2C19 gene. Based on variations within this gene the effectiveness of the drug may be reduced.	Pediatric Conventional Treatment n=22 Participants For children randomized to the genotype-supported arm no genotype will be provided to physicians to assist in dosing.
Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Module	—	—	8.2 score on a scale Interval -3.0 to 21.1	5.4 score on a scale Interval -1.7 to 13.4

Adverse Events

Adult Genotype Guided Treatment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Adult Conventional Treatment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Pediatric Genotype Guided Treatment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Pediatric Conventional Treatment

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

Dr. Larisa Cavallari

University of Florida

Phone: (352) 273-8245

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place