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| Name | Class |
|---|---|
| University of Haifa | OTHER |
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The goal of this study is to develop new methods of administering antidepressant medications that will result in improved drug/placebo separation in randomized controlled trials (RCTs) for Major Depressive Disorder (MDD) and enhanced medication response in open clinical treatment. The highly intensive, weekly visit schedule followed in most antidepressant RCTs radically differs from how antidepressant medications are prescribed in standard clinical practice and is believed to be a major reason why the majority of studies submitted to the Food and Drug Administration (FDA) fail to show a significant difference between medication and placebo. Moreover, a "one size fits all" approach to psychopharmacologic management (i.e., weekly visits for all patients) does not take into account differences between patients that may predispose some individuals to respond positively to frequent follow-up visits, while others may respond negatively or not at all. Clinic visits comprise multiple components that may be therapeutic for depression, including activating patients' behavior, exposing them to medical procedures, permitting social interactions with research staff, and providing supportive meetings with clinicians. Two independent meta-analyses have associated more frequent study visits with increased antidepressant and placebo response as well as decreased separation between medication and placebo. Despite the high costs and potential disadvantages of weekly follow-up visits for patients receiving antidepressant medication, this clinical management strategy has not been studied prospectively to date. It is unknown whether weekly follow-up visits are needed to ensure treatment compliance and patient safety in clinical trials and to what degree contacts with clinicians influence medication and placebo response.
This study utilizes a 2 x 2, double-blind, acute, prospective design randomizing adult
outpatients with MDD to "Research Frequency Management" (RFM, weekly study visits) vs. "Community Frequency Management" (CFM, every 4 weeks study visits) and antidepressant medication vs. placebo. Specifying visit frequency as the independent variable in this study has the distinct advantages of being easily operationalized for research purposes avoiding a priori assumptions about which components of study visits influence antidepressant and placebo response (i.e., behavioral activation vs. doctor-patient relationship vs. medical procedures). Close monitoring of all subjects will be assured by telephone evaluations of individuals randomized to CFM at intervals between monthly visits, and additional study contacts will be scheduled as necessary to maintain patient safety (all extra-protocol contacts will be recorded and included as a variable in outcome analyses). Additionally, subjects will be characterized extensively on clinical, demographic, and psychological measures to pilot the study assessment battery and search for predictor variables influencing the effects of contact frequency on medication and placebo response.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Clinical Frequency Management: Placebo | Placebo Comparator | Study visits monthly (Week 0, 4, and 8), with phone visits every other week (Week 2 and 6). Double-blind, placebo-controlled treatment with escitalopram 10mg/day, raised to 20mg/day, if non-responders at week 4. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. |
|
| Research Frequency Management: Placebo | Placebo Comparator | Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. |
|
| Clinical Frequency Management: Escitalopram | Active Comparator | Study visits monthly (Week 0, 4, and 8), with phone visits every other week (Week 2 and 6). Double-blind, placebo-controlled treatment with escitalopram 10mg/day, raised to 20mg/day, if non-responders at week 4. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. |
|
| Research Frequency Management: Escitalopram | Active Comparator | Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Escitalopram | Drug | Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks) | Scale for depressive symptoms administered by trained rater. The Hamilton is the standard measure of depression severity for clinical trials of antidepressants and was chosen as the primary outcome measure over other depression rating scales to ensure compatibility of study results with our meta-analyses and ongoing studies of expectancy. The scoring is based on the first 24 items of the Hamilton. Sum of the scores of the first 24 items (range from 0 to 74): 0-7 = NORMAL 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression >=23 = Very Severe Depression | Up to 8 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline Hamilton Anxiety Rating Scale 14-item Scale | Scale for anxiety symptoms administered by trained rater. The Hamilton Anxiety is a standard measure of anxiety severity in pharmacotherapy studies that has been shown to have acceptable reliability and validity in studies of depressed patients. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline Clinical Global Impressions | Scales developed to measure the clinician's view of subjects' global functioning before and after initiating a study medication. The Clinical Global Impressions correlates well with other standard outcome measures for depression (e.g., HRSD), is sensitive to change in antidepressant trials, and offers clinically understandable anchor points. 7-point scale: 0 = Not assessed 4 = Moderately ill 1 = Normal, not at all ill 5 = Markedly ill 2 = Borderline mentally ill 6 = Severely ill 3 = Mildly ill 7 = Among the most extremely ill patients |
Inclusion Criteria:
- Inclusion Criteria Method of Ascertainment
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bret Rutherford, MD | New York State Psychiatric Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| New York State Psychiatric Institute | New York | New York | 10032 | United States |
In total, 29 subjects were enrolled. Of the 29 enrolled, 4 subjects did not continue in the study after enrolling. These 4 subjects did not appear for their randomization visit at which they would have been assigned to a study arm. Thus, 29 patients enrolled and 25 patients started.
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| ID | Title | Description |
|---|---|---|
| FG000 | Clinical Frequency Management: Placebo | Study visits monthly (Week 0, 4, and 8), with phone visits every other week (Week 2 and 6). Double-blind, placebo-controlled treatment with escitalopram 10mg/day, raised to 20mg/day, if non-responders at week 4. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient. |
| FG001 | Research Frequency Management: Placebo | Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient. |
| FG002 | Clinical Frequency Management: Escitalopram | Study visits monthly (Week 0, 4, and 8), with phone visits every other week (Week 2 and 6). Double-blind, placebo-controlled treatment with escitalopram 10mg/day, raised to 20mg/day, if non-responders at week 4. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain. |
| FG003 | Research Frequency Management: Escitalopram | Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Clinical Frequency Management: Placebo | Study visits monthly (Week 0, 4, and 8), with phone visits every other week (Week 2 and 6). Double-blind, placebo-controlled treatment with escitalopram 10mg/day, raised to 20mg/day, if non-responders at week 4. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient. |
| Units | Counts |
|---|---|
| Participants |
|
| 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 | Change From Baseline Hamilton Rating Scale for Depression 24-Item Scale to Study Completion (8 Weeks) | Scale for depressive symptoms administered by trained rater. The Hamilton is the standard measure of depression severity for clinical trials of antidepressants and was chosen as the primary outcome measure over other depression rating scales to ensure compatibility of study results with our meta-analyses and ongoing studies of expectancy. The scoring is based on the first 24 items of the Hamilton. Sum of the scores of the first 24 items (range from 0 to 74): 0-7 = NORMAL 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression >=23 = Very Severe Depression | Two CFM, Placebo, two RFM, Placebo, and two CFM, Escitalopram participants did not complete the Hamilton Rating Scale for Depression at Week 8, and so their change from baseline Hamilton Rating scale for Depression score could not be calculated. | Posted | Mean | Standard Deviation | score on a scale | Up to 8 Weeks |
|
Subjects were monitored over a period of 8 weeks.
Subjects in the CFM group were evaluated by study personnel no less frequently than every 2 weeks for 8 weeks. Subjects were monitored for adverse effects, and dose adjustments will be made if indicated during this period of time.
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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 | Clinical Frequency Management: Placebo | Study visits monthly (Week 0, 4, and 8), with phone visits every other week (Week 2 and 6). Double-blind, placebo-controlled treatment with escitalopram 10mg/day, raised to 20mg/day, if non-responders at week 4. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dehydration | Surgical and medical procedures | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anorexia | Psychiatric disorders | Systematic Assessment |
Due to challenges associated with the pandemic, the study was completed with a smaller sample size than originally intended.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Bret Rutherford | New York State Psychiatric Institute | 646-774-8660 | bret.rutherford@nyspi.columbia.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_ICF | Yes | No | Yes | Study Protocol and Informed Consent Form | Dec 17, 2021 | Mar 25, 2022 | Prot_ICF_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 21, 2017 | Feb 17, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D000089983 | Escitalopram |
| ID | Term |
|---|---|
| D011437 | Propylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009570 | Nitriles |
| D001572 |
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|
| Placebo | Drug | A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient. |
|
| Up to 8 Weeks |
| Up to 8 Weeks |
| BG001 | Research Frequency Management: Placebo | Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient. |
| BG002 | Clinical Frequency Management: Escitalopram | Study visits monthly (Week 0, 4, and 8), with phone visits every other week (Week 2 and 6). Double-blind, placebo-controlled treatment with escitalopram 10mg/day, raised to 20mg/day, if non-responders at week 4. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain. |
| BG003 | Research Frequency Management: Escitalopram | Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Hamilton Rating Scale for Depression | Scale for depressive symptoms administered by trained rater. The Hamilton is the standard measure of depression severity for clinical trials of antidepressants and was chosen to ensure compatibility of study results with our meta-analyses and ongoing studies of expectancy. The scoring is based on the first 24 items of the Hamilton. Sum of the scores of the first 24 items (range from 0 to 74): 0-7 = NORMAL 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression >=23 = Very Severe Depression | Mean | Standard Deviation | units on a scale |
|
| Hamilton Anxiety Rating Scale 14-item Scale | Scale for anxiety symptoms administered by trained rater. The Hamilton Anxiety is a standard measure of anxiety severity in pharmacotherapy studies that has been shown to have acceptable reliability and validity in studies of depressed patients. Each of the 14 items is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. | Mean | Standard Deviation | units on a scale |
|
| Clinical Global Impressions Severity | Scales developed to measure the clinician's view of subjects' global functioning before and after initiating a study medication. The Clinical Global Impressions correlates well with other standard outcome measures for depression (e.g., HRSD), is sensitive to change in antidepressant trials, and offers clinically understandable anchor points. 7-point scale: 0 = Not assessed, 1 = Normal, not at all ill, 2 = Borderline mentally ill, 3 = Mildly ill, 4 = Moderately ill, 5 = Markedly ill, 6 = Severely ill, 7 = Among the most extremely ill patients | Mean | Standard Deviation | units on a scale |
|
| Clinical Frequency Management: Placebo |
Study visits monthly (Week 0, 4, and 8), with phone visits every other week (Week 2 and 6). Double-blind, placebo-controlled treatment with escitalopram 10mg/day, raised to 20mg/day, if non-responders at week 4. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient. |
| OG001 | Research Frequency Management: Placebo | Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient. |
| OG002 | Clinical Frequency Management: Escitalopram | Study visits monthly (Week 0, 4, and 8), with phone visits every other week (Week 2 and 6). Double-blind, placebo-controlled treatment with escitalopram 10mg/day, raised to 20mg/day, if non-responders at week 4. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain. |
| OG003 | Research Frequency Management: Escitalopram | Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain. |
|
|
|
| Secondary | Change From Baseline Hamilton Anxiety Rating Scale 14-item Scale | Scale for anxiety symptoms administered by trained rater. The Hamilton Anxiety is a standard measure of anxiety severity in pharmacotherapy studies that has been shown to have acceptable reliability and validity in studies of depressed patients. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. | Two CFM, Placebo, two RFM, Placebo, and three CFM, Escitalopram participants did not complete the Hamilton Anxiety at Week 8, and so their change from baseline Hamilton Anxiety score could not be calculated. | Posted | Mean | Standard Deviation | score on a scale | Up to 8 Weeks |
|
|
|
| Other Pre-specified | Change From Baseline Clinical Global Impressions | Scales developed to measure the clinician's view of subjects' global functioning before and after initiating a study medication. The Clinical Global Impressions correlates well with other standard outcome measures for depression (e.g., HRSD), is sensitive to change in antidepressant trials, and offers clinically understandable anchor points. 7-point scale: 0 = Not assessed 4 = Moderately ill 1 = Normal, not at all ill 5 = Markedly ill 2 = Borderline mentally ill 6 = Severely ill 3 = Mildly ill 7 = Among the most extremely ill patients | Two CFM, Placebo, two RFM, Placebo, and two CFM, Escitalopram participants did not complete the CGI at Week 8, and so their change from baseline CGI score could not be calculated. | Posted | Mean | Standard Deviation | score on a scale | Up to 8 Weeks |
|
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 2 |
| 5 |
| EG001 | Research Frequency Management: Placebo | Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Placebo: A placebo (or dummy pill) is an inert (inactive) substance, typically a tablet, capsule or other dose form that does not contain an active drug ingredient. | 0 | 7 | 0 | 7 | 6 | 7 |
| EG002 | Clinical Frequency Management: Escitalopram | Study visits monthly (Week 0, 4, and 8), with phone visits every other week (Week 2 and 6). Double-blind, placebo-controlled treatment with escitalopram 10mg/day, raised to 20mg/day, if non-responders at week 4. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain. | 0 | 5 | 0 | 5 | 1 | 5 |
| EG003 | Research Frequency Management: Escitalopram | Weekly study visits, treatment with double-blind, placebo controlled escitalopram 10 mg/day, raised to 20mg/day at week 4 if non-responders. If they respond, will be treated in a 3-month Continuation Phase with monthly site visits. Escitalopram: Escitalopram is a Selective Serotonin Reuptake Inhibitor (SSRI) medication that appears to help with symptoms of depression by increasing the availability of specific chemicals in the brain. | 0 | 8 | 1 | 8 | 6 | 8 |
| Body Pain | General disorders | Systematic Assessment |
|
| Bradycardia | Cardiac disorders | Systematic Assessment |
|
| Confusion | Psychiatric disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Diaphoresis | General disorders | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Dizziness | General disorders | Systematic Assessment |
|
| Drowsiness | General disorders | Systematic Assessment |
|
| Dry Mouth | General disorders | Systematic Assessment |
|
| Excitement | Psychiatric disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | Systematic Assessment |
|
| Headache | General disorders | Systematic Assessment |
|
| Insomnia | General disorders | Systematic Assessment |
|
| Memory Loss | Psychiatric disorders | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Orgasm Delay | Reproductive system and breast disorders | Systematic Assessment |
|
| Palpitations | Cardiac disorders | Systematic Assessment |
|
| Shortness of Breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Suicidal Ideation | Psychiatric disorders | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | Systematic Assessment |
|
| Tremor | Nervous system disorders | Systematic Assessment |
|
| Urinary Frequency/Urgency | Renal and urinary disorders | Systematic Assessment |
|
| Vivid Dreams | Psychiatric disorders | Systematic Assessment |
|
| Weakness | General disorders | Systematic Assessment |
|
| Weight Gain | General disorders | Systematic Assessment |
|
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| Benzofurans |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |