Aprepitant for the Relief of Nausea in Patients With Chronic Nausea and Vomiting of Presumed Gastric Origin: A Multicenter, Randomized, Double-Masked, Placebo-Controlled Trial

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)8 sites in 1 country126 target enrollmentApril 2013

ConditionsGastroparesis

InterventionsAprepitant Placebo

DrugsAprepitant Placebo

Overview

Phase: Phase 2
Intervention: Aprepitant
Conditions: Gastroparesis
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Enrollment: 126
Locations: 8
Primary Endpoint: Number of Participants With Improvement in Nausea
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The principal objective of this multicenter, randomized, placebo-controlled trial is to evaluate whether 4 weeks of treatment with aprepitant will improve nausea as compared with placebo in patients with symptoms of chronic nausea and vomiting of presumed gastric origin.

Detailed Description

APRON is a multicenter, randomized, double-masked, placebo controlled trial of 4 weeks of treatment with aprepitant or placebo for patients with symptoms of gastroparesis and related disorders. Screening for eligibility and collection of baseline data will span up to 4 weeks after obtaining informed consent and registration. Eligible patients will consist of patients with symptoms of gastroparesis and will be randomized to either aprepitant (125 mg per day) or placebo for 4 weeks. The symptoms will be measured with the Gastroparesis Cardinal Symptom Index Daily Diary (GCSIDD) for one week at baseline and for four weeks after randomization. In addition, the nausea symptom will be measured daily on a 0 to 100 mm visual analog scale (VAS) for one week at baseline and daily for four weeks after randomization. There will be a 2 week washout period at the end of the treatment to ensure patient safety following the end of treatment.

Registry

clinicaltrials.gov

Start Date

April 2013

End Date

September 2015

Last Updated

6 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age 18 years or older at registration
•Gastric emptying scintigraphy within 2 years of registration
•Normal upper endoscopy or upper GI series within 2 years of registration
•Symptoms of chronic nausea or vomiting compatible with gastroparesis or other functional gastric disorder for at least 6 months (does not have to be contiguous) prior to registration with Gastroparesis Cardinal Symptom Index (GCSI) score of greater than or equal to 21
•Significant nausea defined with a visual analog scale (VAS) score of greater than or equal to 25 mm on a 0 to 100 mm scale

Exclusion Criteria

•Another active disorder which could explain symptoms in the opinion of the investigator
•Use of narcotics more than 3 days per week
•Significant hepatic injury as defined by significant alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations of greater than 2x the upper limit of normal (ULN) or a Child-Pugh score of 10 or greater
•Contraindications to aprepitant such as hypersensitivity or allergy
•Concurrent use of warfarin, pimozide, terfenadine, astemizole, or cisapride
•Pregnancy or nursing
•Any other condition, which in the opinion of the investigator would impede compliance or hinder the completion of the study
•Failure to give informed consent

Arms & Interventions

Aprepitant

Aprepitant 125 mg per day

Intervention: Aprepitant

Aprepitant-placebo

Placebo aprepitant 125mg per day

Intervention: Placebo

Outcomes

Primary Outcomes

Number of Participants With Improvement in Nausea

Time Frame: 4 weeks

The primary outcome measure is a binary (0,1) variable indicating improvement in nausea or not in the mean of available visual analog scale (VAS) scores over the 28 day treatment period compared to the mean of VAS scores during the 7 day baseline period. The criteria for improvement are either a 25 mm or more reduction in mean VAS or attaining a mean VAS during the treatment period of \< 25 mm.

Secondary Outcomes

Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): GCSI Total Score(4 weeks)
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Nausea (Hours)(4 weeks)
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Vomiting (No. Episodes)(4 weeks)
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Retching (No. Episodes)(4 weeks)
Liver Enzymes and Proteins: Total Protein(4 weeks)
Hemoglobin A1c (HbA1c)(4 weeks)
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Nausea Severity(4 weeks)
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Vomiting Severity(4 weeks)
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Upper Abdominal Pain Severity(4 weeks)
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Excessive Fullness Severity(4 weeks)
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Early Satiety Severity(4 weeks)
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Bloating Severity(4 weeks)
Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD): Overall Symptom Severity(4 weeks)
Clinical Global Patient Impression Score (Patient-rated)(4 weeks)
Liver Enzymes and Proteins: Alanine Aminotransferase (ALT)(4 weeks)
Liver Enzymes and Proteins: Aspartate Aminotransferase (AST)(4 weeks)
Glucose(4 weeks)
Liver Enzymes and Proteins: Albumin(4 weeks)
Hemoglobin(4 weeks)
Hematocrit(4 weeks)
White Blood Cell Count (WBC)(4 weeks)
Red Blood Cell Count (RBC)(4 weeks)
Platelet Count(4 weeks)
Carbon Dioxide(4 weeks)
Chloride(4 weeks)
Sodium(4 weeks)
Potassium(4 weeks)
Calcium(4 weeks)
Blood Urea Nitrogen (BUN)(4 weeks)
Magnesium(4 weeks)
Creatinine(4 weeks)
PAGI-SYM Severity Index: Gastroparesis Cardinal Symptom Index (GCSI) Score(4 weeks)
PAGI-SYM Severity Index: Nausea/Vomiting Severity Subscore(4 weeks)
PAGI-SYM Severity Index: Fullness/Early Satiety Subscore(4 weeks)
PAGI-SYM Severity Index: Bloating Subscore(4 weeks)
PAGI-SYM Severity Index: Upper Abdominal Pain Subscore(4 weeks)
PAGI-SYM Severity Index: GERD Subscore(4 weeks)
PAGI-SYM Severity Index: Nausea Severity(4 weeks)
PAGI-SYM Severity Index: Vomiting Severity(4 weeks)
PAGI-SYM Severity Index: Retching Severity(4 weeks)
PAGI-SYM Severity Index: Stomach Fullness Severity(4 weeks)
PAGI-SYM Severity Index: Unable to Finish Meal Severity(4 weeks)
PAGI-SYM Severity Index: Excessive Fullness Severity(4 weeks)
PAGI-SYM Severity Index: Loss of Appetite Severity(4 weeks)
PAGI-SYM Severity Index: Bloating Severity(4 weeks)
PAGI-SYM Severity Index: Stomach Distention Severity(4 weeks)
PAGI-SYM Severity Index: Upper Abdominal Pain Severity(4 weeks)
PAGI-SYM Severity Index: Upper Abdominal Discomfort Severity(4 weeks)
PAGI-SYM Severity Index: Lower Abdominal Pain Severity(4 weeks)
PAGI-SYM Severity Index: Lower Abdominal Discomfort Severity(4 weeks)
PAGI-SYM Severity Index: Heartburn During the Day Severity(4 weeks)
PAGI-SYM Severity Index: Heartburn When Lying Down Severity(4 weeks)
PAGI-SYM Severity Index: Chest Discomfort During the Day Severity(4 weeks)
PAGI-SYM Severity Index: Chest Discomfort During Sleep Time Severity(4 weeks)
PAGI-SYM Severity Index: Regurgitation During the Day Severity(4 weeks)
PAGI-SYM Severity Index: Regurgitation When Lying Down Severity(4 weeks)
PAGI-SYM Severity: Bitter Taste Severity(4 weeks)
PAGI-SYM Severity Index: Constipation Severity(4 weeks)
PAGI-SYM Severity Index: Diarrhea Severity(4 weeks)
Gastrointestinal Symptom Rating Scale (GSRS): Total Score(4 weeks)
Gastrointestinal Symptom Rating Scale (GSRS): Reflux Score(4 weeks)
Gastrointestinal Symptom Rating Scale (GSRS): Abdominal Pain Score(4 week)
Gastrointestinal Symptom Rating Scale (GSRS): Indigestion Score(4 weeks)
Gastrointestinal Symptom Rating Scale (GSRS): Diarrhea Score(4 weeks)
Gastrointestinal Symptom Rating Scale (GSRS): Constipation Score(4 weeks)
Brief Pain Inventory: Severity Score(4 weeks)
Brief Pain Inventory: Interference Score(4 weeks)
Beck Depression Inventory (BDI) Score(4 weeks)
State-Trait Anxiety Inventory (STAI): State Anxiety Score(4 weeks)
State-Trait Anxiety Inventory (STAI): Trait Anxiety Score(4 weeks)
Satiety Test, Volume Consumed(4 weeks)
Electrogastrography (EGG): Bradygastria (1-<2.5 Cpm) at 4 Weeks, Baseline Measurement(4 weeks)
Electrogastrography (EGG): Bradygastria (1-<2.5 Cpm) at 4 Weeks, 0-30 Post-satiety Measurement(4 weeks)
Electrogastrography (EGG): Normogastria (2.5-<3.8 Cpm) at 4 Weeks, Baseline Measurement(4 weeks)
Electrogastrography (EGG): Normogastria (2.5-<3.8 Cpm) at 4 Weeks, 0-30 Post-satiety Measurement(4 weeks)
Electrogastrography (EGG): Tachygastria (3.8-10 Cpm) at 4 Weeks, 0-30 Post-satiety Measurement(4 weeks)
Electrogastrography (EGG): Tachygastria (3.8-10 Cpm) at 4 Weeks, Baseline Measurement(4 weeks)
Electrogastrography (EGG): Duodenal (>10-15 Cpm) at 4 Weeks, 0-30 Post-satiety Measurement(4 weeks)
Electrogastrography (EGG): Duodenal (>10-15 Cpm) at 4 Weeks, Baseline Measurement(4 weeks)