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| Name | Class |
|---|---|
| Brigham and Women's Hospital | OTHER |
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The investigators are doing this research study to find out if giving a drug called prasugrel, which is used to prevent blood clots, can reduce reactions to aspirin in people with aspirin exacerbated respiratory disease (AERD), and to learn why taking aspirin every day can work as a treatment for people with AERD. People with AERD have symptoms of asthma, severe runny nose, polyps in the nose, and develop allergic reactions if they take medications like aspirin.
People with AERD can be desensitized to aspirin in order to be able to safely use it daily, but the investigators do not know if prasugrel may prevent reactions to aspirin and provide a safer way for people with AERD to tolerate aspirin.
The investigators also want to understand what is different about the cells and urine from subjects who have AERD, in comparison to subjects who have asthma but do not have AERD and subjects who have allergic rhinitis but do not have asthma. Lastly, the investigators want to understand how aspirin acts differently in subjects who have AERD, in comparison to subjects who have asthma but do not have AERD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo then Prasugrel | Experimental | Subjects with AERD first received placebo oral tablet for 4 weeks prior to their aspirin challenge/desensitization. After aspirin challenge/desensitization subjects were discharged to home to washout the study drug from the first treatment phase. At the end of the 2-week washout period, subjects crossed over to the alternate treatment for 4 weeks of Prasugrel oral tablets [ (5 mg (for patients <60kg) or 10mg (> 60kg) daily, following a 60mg loading dose)] and returned for the second aspirin challenge. Because no period effect was observed, data obtained from all subjects while on placebo from either visit 2 or 3 were combined. |
|
| Prasugrel then Placebo | Experimental | Subjects with AERD first received prasugrel oral tablets [ (5 mg (for patients <60kg) or 10mg (> 60kg) daily, following a 60mg loading dose)] prior to their aspirin challenge/desensitization. After aspirin challenge/desensitization subjects were discharged to home to washout the study drug from the first treatment phase. At the end of the 2-week washout period, subjects crossed over to the alternate treatment for 4 weeks of Placebo oral tablet. Because no period effect was observed, data obtained from all subjects while on Prasugrel from either visit 2 or 3 were combined. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo Oral Tablet | Drug | Participants will take a 60 mg loading dose. After they will take 10 mg by mouth daily if they weigh >60kg or 5 mg by mouth daily if they weigh <60 kg. They will take the drug for 4 weeks prior to the aspirin challenge/desensitization. |
| Measure | Description | Time Frame |
|---|---|---|
| Difference in PD2 (Provocative Dose of Aspirin That Elicits an Increase in Nasal Symptom Score of 2 During an Aspirin Challenge) on Prasugrel Versus Placebo | The PD2 is the provocative dose of aspirin that elicits an increase in nasal symptom score of 2 during an aspirin challenge. The PD2 is calculated by: inverse〖log〗_10 (((2-(PrevTNSS-BaselineTNSS))×(〖log〗_10 ProvocDose-〖log〗_10 PrevDose))/((MaxTNSS-BaselineTNSS)-(PrevTNSS-BaselineTNSS) )+(〖log〗_10 PrevDose)) | Difference in PD2 (provocative dose of aspirin that elicits an increase in nasal symptom score of 2 during an aspirin challenge) between Visits 2 and 3 (weeks 8 and 14), calculated at visit 3 |
| Change From Baseline Expression Levels of COX-2 Transcript and Protein in Peripheral Blood Leukocytes of Subjects With AERD After 8 Weeks of Treatment With Aspirin. | This study will compare this outcome within each participant between baseline (established at Visit 1, prior to initiation of prasugrel therapy) and at the completion of 8 weeks of aspirin therapy. | Evaluated at visits 1 and 4 (weeks 4 and 22) |
| Measure | Description | Time Frame |
|---|---|---|
| Difference in Participant's Provocative Dose of Aspirin When Pretreated With Prasugrel Versus Placebo | We will monitor the dose of aspirin at which the participant shows symptoms (increased discomfort, 15% drop in FEV1) during the aspirin challenge/desensitization. We will compare the provocative aspirin dose obtained from the aspirin challenge occurring after pretreatment with prasugrel to the dose obtained after pretreatment with placebo. |
| Measure | Description | Time Frame |
|---|---|---|
| Baseline Differences in Platelet Chemistry in Subjects With AERD Compared to Controls | To determine if there are baseline differences in the percentages of activated platelets, platelet-leukocyte aggregates, or the plasma levels of soluble platelet products in subjects with AERD, compared to aspirin tolerant asthmatics (ATA) and non-asthmatic controls. | Evaluated at visit 1 (week 4) |
Inclusion Criteria for Participants with AERD:
Inclusion Criteria for Participants who are Aspirin Tolerant Asthmatics:
Inclusion Criteria for Non Asthmatics with Allergic Rhinitis:
Exclusion Criteria for participants with AERD:
Exclusion Criteria for Participants with Aspirin Tolerant Asthma and Non Asthmatics with Allergic Rhinitis:
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| Name | Affiliation | Role |
|---|---|---|
| Elliot Israel, MD | Brigham and Women's Hospital | Principal Investigator |
| Joshua Boyce, MD | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Asthma Research Center | Boston | Massachusetts | 02115 | United States |
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| Label | URL |
|---|---|
| Click here for more info. | View source |
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46 of whom underwent randomization per protocol, and 40 of whom completed the trial and were analyzed.
A total of 51 potential participants were screened at Brigham and Women's Hospital.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo Then Prasugrel | Subjects with AERD first received placebo oral tablet for 4 weeks prior to their aspirin challenge/desensitization. After aspirin challenge/desensitization subjects were discharged to home to washout the study drug from the first treatment phase. At the end of the 2-week washout period, subjects crossed over to the alternate treatment for 4 weeks of Prasugrel oral tablets [ (5 mg (for patients <60kg) or 10mg (> 60kg) daily, following a 60mg loading dose)] and returned for the second aspirin challenge. Because no period effect was observed, data obtained from all subjects while on placebo from either visit 2 or 3 were combined. |
| FG001 | Prasugrel Then Placebo | Subjects with AERD first received prasugrel oral tablets [ (5 mg (for patients <60kg) or 10mg (> 60kg) daily, following a 60mg loading dose)] prior to their aspirin challenge/desensitization. After aspirin challenge/desensitization subjects were discharged to home to washout the study drug from the first treatment phase. At the end of the 2-week washout period, subjects crossed over to the alternate treatment for 4 weeks of Placebo oral tablet. Because no period effect was observed, data obtained from all subjects while on Prasugrel from either visit 2 or 3 were combined. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (4 Weeks) |
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| Washout (2 Weeks) |
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| Second Intervention |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Participants who were randomized to receive either Prasugrel or Placebo oral tablets and who successfully completed both treatment assignments. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Difference in PD2 (Provocative Dose of Aspirin That Elicits an Increase in Nasal Symptom Score of 2 During an Aspirin Challenge) on Prasugrel Versus Placebo | The PD2 is the provocative dose of aspirin that elicits an increase in nasal symptom score of 2 during an aspirin challenge. The PD2 is calculated by: inverse〖log〗_10 (((2-(PrevTNSS-BaselineTNSS))×(〖log〗_10 ProvocDose-〖log〗_10 PrevDose))/((MaxTNSS-BaselineTNSS)-(PrevTNSS-BaselineTNSS) )+(〖log〗_10 PrevDose)) | Posted | Mean | Standard Error | mg | Difference in PD2 (provocative dose of aspirin that elicits an increase in nasal symptom score of 2 during an aspirin challenge) between Visits 2 and 3 (weeks 8 and 14), calculated at visit 3 |
|
Adverse events were reported from the time of patient enrollment through study completion, an average of 20 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Subjects with AERD who received placebo oral tablets either the first or last 4 weeks of the study. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bruising | Blood and lymphatic system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tanya Laidlaw | Brigham and Women's Hospital | 617-525-1034 | tlaidlaw@bwh.harvard.edu |
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| ID | Term |
|---|---|
| D055963 | Asthma, Aspirin-Induced |
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
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| ID | Term |
|---|---|
| D000068799 | Prasugrel Hydrochloride |
| ID | Term |
|---|---|
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D010879 | Piperazines |
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|
| Prasugrel Oral Tablet | Drug | Participants will take a 60 mg loading dose. After they will take 10 mg by mouth daily if they weigh >60kg or 5 mg by mouth daily if they weigh <60 kg. They will take the drug for 4 weeks prior to the aspirin challenge/desensitization. |
|
|
| Evaluated at visits 2 and 3 (weeks 8 and 14) |
| Change in Total Nasal Symptom Score(TNSS)From Baseline to Peak During Aspirin Challenge on Placebo Versus Prasugrel. | The primary outcome in Part 1 will be the maximum Total Nasal Symptom Score (TNSS) attained for subjects with AERD during the clinical reaction to aspirin challenge. The primary analysis will compare this outcome within each participant after treatment with prasugrel versus placebo. Nasal symptoms including congestion, rhinorrhea, runny nose, itchy nose, sneezing, itchy eyes, teary eyes, itchy ears/throat, and eye redness were assessed on a 0- to 5-point scale (0, none-5, very severe) in response to the provocative dose of aspirin during aspirin challenge/desensitization and summed together to generate the TNSS score (range 0-40). | Data obtained at visits 2 and 3 (weeks 8 and 14) and change calculated at visit 3 |
| Change in Urinary LTE4 During Aspirin Challenge on Placebo Versus Prasugrel | We will compare the participant's Leukotriene E4 (LTE4) obtained from the aspirin challenge done after pretreatment with prasugrel, the aspirin challenge done after pretreatment with placebo. | Change from visits 2 at visit 3 (weeks 8, 14), calculated and reported at visit 3 |
| Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) Measurement After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks | We will note difference in the fractional exhaled nitric oxide (FeNO) obtained before any treatment ( baseline ) and after one day Aspirin desensitization followed by 8 weeks Aspirin treatment ( 650 mg oral aspirin tablet twice daily ) | Evaluated at baseline and reported at 8 weeks |
| Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Score After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks | We will note difference in the Asthma Control Questionnaire-7 (ACQ-7) score [ The ACQ has 7 questions on a 7-point scale (minimum score of 0=no impairment, maximum score of 6= maximum impairment)] obtained before any treatment ( baseline ) and after one day Aspirin desensitization followed by 8 weeks Aspirin treatment ( 650 mg oral aspirin tablet twice daily ) | Evaluated at baseline and reported at 8 weeks |
| Change From Baseline in Prostaglandin Metabolites (PGD-M) Measurement After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks | We will note difference in the Prostaglandin metabolites (PGD-M) measurement obtained before any treatment ( baseline ) and after one day Aspirin desensitization followed by 8 weeks Aspirin treatment ( 650 mg oral aspirin tablet twice daily ) | Evaluated at baseline and reported at 8 weeks |
| Effect of Prasugrel on Platelet Chemistry in Subjects With AERD During Aspirin Challenge. | To determine if treatment with prasugrel changes the baseline percentages of activated platelets or platelet-leukocyte aggregates or changes the plasma levels of soluble platelet products during clinical reaction to aspirin | Evaluated at visit 2 and 3 (week 8 and 14) |
| Lost to Follow-up |
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| NOT COMPLETED |
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| NOT COMPLETED |
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| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
|
| Prasugrel |
Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study. |
|
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| Primary | Change From Baseline Expression Levels of COX-2 Transcript and Protein in Peripheral Blood Leukocytes of Subjects With AERD After 8 Weeks of Treatment With Aspirin. | This study will compare this outcome within each participant between baseline (established at Visit 1, prior to initiation of prasugrel therapy) and at the completion of 8 weeks of aspirin therapy. | The planned experimental protocol for COX-2 analysis at the lab bench was unsuccessful, therefore no data was collected for this Outcome Measure | Posted | Evaluated at visits 1 and 4 (weeks 4 and 22) |
|
|
| Secondary | Difference in Participant's Provocative Dose of Aspirin When Pretreated With Prasugrel Versus Placebo | We will monitor the dose of aspirin at which the participant shows symptoms (increased discomfort, 15% drop in FEV1) during the aspirin challenge/desensitization. We will compare the provocative aspirin dose obtained from the aspirin challenge occurring after pretreatment with prasugrel to the dose obtained after pretreatment with placebo. | Posted | Mean | Standard Error | mg | Evaluated at visits 2 and 3 (weeks 8 and 14) |
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| Secondary | Change in Total Nasal Symptom Score(TNSS)From Baseline to Peak During Aspirin Challenge on Placebo Versus Prasugrel. | The primary outcome in Part 1 will be the maximum Total Nasal Symptom Score (TNSS) attained for subjects with AERD during the clinical reaction to aspirin challenge. The primary analysis will compare this outcome within each participant after treatment with prasugrel versus placebo. Nasal symptoms including congestion, rhinorrhea, runny nose, itchy nose, sneezing, itchy eyes, teary eyes, itchy ears/throat, and eye redness were assessed on a 0- to 5-point scale (0, none-5, very severe) in response to the provocative dose of aspirin during aspirin challenge/desensitization and summed together to generate the TNSS score (range 0-40). | Posted | Mean | Standard Error | units on scale | Data obtained at visits 2 and 3 (weeks 8 and 14) and change calculated at visit 3 |
|
|
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| Secondary | Change in Urinary LTE4 During Aspirin Challenge on Placebo Versus Prasugrel | We will compare the participant's Leukotriene E4 (LTE4) obtained from the aspirin challenge done after pretreatment with prasugrel, the aspirin challenge done after pretreatment with placebo. | Posted | Mean | Standard Deviation | percentage change from baseline | Change from visits 2 at visit 3 (weeks 8, 14), calculated and reported at visit 3 |
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| Secondary | Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) Measurement After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks | We will note difference in the fractional exhaled nitric oxide (FeNO) obtained before any treatment ( baseline ) and after one day Aspirin desensitization followed by 8 weeks Aspirin treatment ( 650 mg oral aspirin tablet twice daily ) | This was assessed across all participants with no planned comparisons between placebo and prasugrel. | Posted | Mean | Standard Deviation | parts per billion | Evaluated at baseline and reported at 8 weeks |
|
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|
| Secondary | Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Score After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks | We will note difference in the Asthma Control Questionnaire-7 (ACQ-7) score [ The ACQ has 7 questions on a 7-point scale (minimum score of 0=no impairment, maximum score of 6= maximum impairment)] obtained before any treatment ( baseline ) and after one day Aspirin desensitization followed by 8 weeks Aspirin treatment ( 650 mg oral aspirin tablet twice daily ) | This was assessed across all participants with no planned comparisons between placebo and prasugrel. | Posted | Mean | Standard Deviation | score on a scale | Evaluated at baseline and reported at 8 weeks |
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|
| Secondary | Change From Baseline in Prostaglandin Metabolites (PGD-M) Measurement After Aspirin Desensitization and High Dose Aspirin Treatment at 8 Weeks | We will note difference in the Prostaglandin metabolites (PGD-M) measurement obtained before any treatment ( baseline ) and after one day Aspirin desensitization followed by 8 weeks Aspirin treatment ( 650 mg oral aspirin tablet twice daily ) | This was assessed across all participants with no planned comparisons between placebo and prasugrel. | Posted | Mean | Standard Deviation | ng/mg creatinine | Evaluated at baseline and reported at 8 weeks |
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| Other Pre-specified | Baseline Differences in Platelet Chemistry in Subjects With AERD Compared to Controls | To determine if there are baseline differences in the percentages of activated platelets, platelet-leukocyte aggregates, or the plasma levels of soluble platelet products in subjects with AERD, compared to aspirin tolerant asthmatics (ATA) and non-asthmatic controls. | Not Posted | Evaluated at visit 1 (week 4) | Participants |
| Other Pre-specified | Effect of Prasugrel on Platelet Chemistry in Subjects With AERD During Aspirin Challenge. | To determine if treatment with prasugrel changes the baseline percentages of activated platelets or platelet-leukocyte aggregates or changes the plasma levels of soluble platelet products during clinical reaction to aspirin | Not Posted | Evaluated at visit 2 and 3 (week 8 and 14) | Participants |
| 0 |
| 43 |
| 0 |
| 43 |
| 13 |
| 43 |
| EG001 | Prasugrel | Subjects with AERD who received prasugrel oral tablets either the first or last 4 weeks of the study. | 0 | 42 | 0 | 42 | 13 | 42 |
| Upper Respiratory Tract Infection/Sinusitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Worsening of Asthma | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Muscle injury/Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Throat Infection | Infections and infestations | Systematic Assessment |
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| Accidental ingestion of NSAID | Injury, poisoning and procedural complications | Systematic Assessment |
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| Systematic Reaction to Aspirin Challenge | Injury, poisoning and procedural complications | Systematic Assessment |
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| Skin Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Conjunctivitis | Eye disorders | Systematic Assessment |
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| Ear Infection | Ear and labyrinth disorders | Systematic Assessment |
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| Finger tingling/Numbness | Nervous system disorders | Systematic Assessment |
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| Joint Stiffness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Light-Headedness | Nervous system disorders | Systematic Assessment |
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| Lower leg edema | Blood and lymphatic system disorders | Systematic Assessment |
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| Mood Change | Psychiatric disorders | Systematic Assessment |
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| Spider Bite | Injury, poisoning and procedural complications | Systematic Assessment |
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| Stomach Pain | Gastrointestinal disorders | Systematic Assessment |
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| Urinary Tract Infection | Renal and urinary disorders | Systematic Assessment |
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| Viral Gastroenteritis | Gastrointestinal disorders | Systematic Assessment |
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| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D004342 | Drug Hypersensitivity |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |