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| Name | Class |
|---|---|
| Premier Research | OTHER |
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A prospective, double-blind, randomized, placebo and active controlled, multi-center, parallel group study comparing remimazolam to placebo, with an additional open label arm for midazolam, in patients undergoing a bronchoscopy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Remimazolam | Experimental | Double-blind Remimazolam arm: 5 mg iv for sedation induction, and 2.5 mg iv top-ups for sedation maintenance. Fentanyl pre-treatment: 25-50 μg (or less for elderly/disabled subjects), and 25 μg top-up doses |
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| Placebo | Placebo Comparator | Double-blind placebo arm as inactive control Fentanyl pre-treatment: 25-50 μg (or less for elderly/disabled subjects), and 25 μg top-up doses |
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| Midazolam | Active Comparator | Open-label Midazolam arm: 1.75 mg* iv for sedation induction and 1.0 mg* iv for sedation maintenance. *1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill. Fentanyl pre-treatment: 25-50 μg (or less for elderly/disabled subjects), and 25 μg top-up doses |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Remimazolam | Drug | For induction and maintenance of sedation |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With a Successful Procedure | Success of Procedure measured by completion of bronchoscopy, no requirement for an alternative rescue sedative medication and no requirement for more than 5 doses of study medication within any 15 minute period in the blinded arms (remimazolam/placebo) or no requirement for more than 3 doses within any 12 minute window in the open-label midazolam arm. | From first dose of study drug to removal of bronchoscope (average time not known) |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Start of Procedure | The time from the first dose of study drug until bronchoscope insertion on Day 1 | From first dose of study drug until insertion of the bronchoscope |
| Time to Fully Alert |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gerard Silvestri, MD | Medical University of South Carolina, US | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pab Clinical Research | Brandon | Florida | 33511 | United States | ||
| Sun City Office |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30292760 | Result | Pastis NJ, Yarmus LB, Schippers F, Ostroff R, Chen A, Akulian J, Wahidi M, Shojaee S, Tanner NT, Callahan SP, Feldman G, Lorch DG Jr, Ndukwu I, Pritchett MA, Silvestri GA; PAION Investigators. Safety and Efficacy of Remimazolam Compared With Placebo and Midazolam for Moderate Sedation During Bronchoscopy. Chest. 2019 Jan;155(1):137-146. doi: 10.1016/j.chest.2018.09.015. Epub 2018 Oct 4. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Remimazolam | Remimazolam iv 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance. |
| FG001 | Placebo | Placebo iv as inactive control arm |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 3, 2016 | Feb 15, 2019 |
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| Placebo | Drug | Inactive control arm |
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| Midazolam | Drug | For induction and maintenance of sedation |
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The time to fully alert defined as time to first of 3 consecutive Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scores after the end of the bronchoscopy procedure (bronchoscope out).
MOAA/S scores: 5 = Responds readily to name spoken in normal tone [alert], 4 =Lethargic response to name spoken in normal tone, 3 = Responds only after name is called loudly and/or repeatedly, 2 = Responds only after mild prodding or shaking, 1 = Responds only after painful trapezius squeeze, 0 = Does not respond to painful trapezius squeeze.
MOAA/S scores were assessed by the investigators.
| From the last dose of study drug or rescue sedative AND from end of bronchoscopy until the patient has recovered to fully alert |
| Time to Ready for Discharge | Time from the last dose of study drug or rescue sedative and from the end of bronchoscopy until discharge (defined as the ability to walk unassisted) | After the last dose of study drug AND after the end of the bronchoscopy, until discharge |
| Sun City Center |
| Florida |
| 33573 |
| United States |
| Laporte County Institute For Clinical Research | Michigan City | Indiana | 46360 | United States |
| The Johns Hopkins Center for Interventional and Pulmonary Care | Baltimore | Maryland | 21287 | United States |
| Washington University School of Medicine/Barnes-Jewish Hospital | St Louis | Missouri | 63110 | United States |
| Unc Division of Pulmonary and Critical Care | Chapel Hill | North Carolina | 27599 | United States |
| Duke University | Durham | North Carolina | 27710 | United States |
| Pinehurst Medical Clinic | Pinehurst | North Carolina | 28374 | United States |
| Wake Forest Baptist Health | Winston-Salem | North Carolina | 27157 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| S. Carolina Pharmaceutical Research | Spartanburg | South Carolina | 29303 | United States |
| Pulmonary Associates of Richmond | Richmond | Virginia | 23225 | United States |
| Virginia Commonwealth University | Richmond | Virginia | 23298 | United States |
| Multicare Institute For Research & Innovation | Tacoma | Washington | 98405 | United States |
| FG002 | Midazolam | Midazolam iv 1.75 mg* for sedation induction and 1.0 mg* for sedation maintenance. *1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill. |
| Safety Population | All randomized patients who received any amount of the trial drug and were analyzed as treated |
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| Complete Trial Treatment Period |
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| COMPLETED |
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| NOT COMPLETED |
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Baseline Analysis Population is the Safety Population
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| ID | Title | Description |
|---|---|---|
| BG000 | Remimazolam | Remimazolam iv 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance. |
| BG001 | Placebo | Placebo iv as inactive control arm |
| BG002 | Midazolam | Midazolam iv 1.75 mg* for sedation induction and 1.0 mg* for sedation maintenance. *1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill. |
| BG003 | Total | Total of all reporting groups |
| 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, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Height | Mean | Standard Deviation | cm |
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| Weight | Mean | Standard Deviation | kg |
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| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
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| 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Number of Participants With a Successful Procedure | Success of Procedure measured by completion of bronchoscopy, no requirement for an alternative rescue sedative medication and no requirement for more than 5 doses of study medication within any 15 minute period in the blinded arms (remimazolam/placebo) or no requirement for more than 3 doses within any 12 minute window in the open-label midazolam arm. | All patients who were randomized and were analyzed as randomized. | Posted | Count of Participants | Participants | From first dose of study drug to removal of bronchoscope (average time not known) |
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| Secondary | Time to Start of Procedure | The time from the first dose of study drug until bronchoscope insertion on Day 1 | All patients who were randomized and were analyzed as randomized. | Posted | Median | 95% Confidence Interval | minutes | From first dose of study drug until insertion of the bronchoscope |
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| Secondary | Time to Fully Alert | The time to fully alert defined as time to first of 3 consecutive Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scores after the end of the bronchoscopy procedure (bronchoscope out). MOAA/S scores: 5 = Responds readily to name spoken in normal tone [alert], 4 =Lethargic response to name spoken in normal tone, 3 = Responds only after name is called loudly and/or repeatedly, 2 = Responds only after mild prodding or shaking, 1 = Responds only after painful trapezius squeeze, 0 = Does not respond to painful trapezius squeeze. MOAA/S scores were assessed by the investigators. | Patients who do not reach the endpoint are censored at last MOAAS | Posted | Median | 95% Confidence Interval | minutes | From the last dose of study drug or rescue sedative AND from end of bronchoscopy until the patient has recovered to fully alert |
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| Secondary | Time to Ready for Discharge | Time from the last dose of study drug or rescue sedative and from the end of bronchoscopy until discharge (defined as the ability to walk unassisted) | Patients who do not reach the endpoint are censored at last MOAAS | Posted | Median | 95% Confidence Interval | minutes | After the last dose of study drug AND after the end of the bronchoscopy, until discharge |
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Treatment-emergent Adverse Events were collected from Day 1 until end of Follow-Up (Day 4 [+3/-1 days]). TEAEs were followed-up until events were resolved, became stable or could be explained by another known cause(s)
Total number of participants affected with Other (Not Including Serious) Adverse Events represents any participant in the trial with a TEAE. The number of participants with Preferred Term (PT)TEAEs represents participants with non-serious TEAEs reported with a threshold of 5% in any of the arms
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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 | Remimazolam | Remimazolam iv 5 mg for sedation induction, and 2.5 mg top-ups for sedation maintenance. | 0 | 303 | 17 | 303 | 268 | 303 |
| EG001 | Placebo | Placebo iv as inactive control arm | 0 | 59 | 4 | 59 | 52 | 59 |
| EG002 | Midazolam | Midazolam iv 1.75 mg* for sedation induction and 1.0 mg* for sedation maintenance. *1.0 mg for induction and 0.5 mg for maintenance in adults over 60, debilitated or chronically ill. | 0 | 69 | 0 | 69 | 63 | 69 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Organising pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Pneumomediastinum | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Atrial fibrillation | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Atrial tachycardia | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Bradycardia | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Lobar pneumonia | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Confusional state | Psychiatric disorders | MedDRA 18.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypotension | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
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| Diastolic hypertension | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
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| Systolic hypertension | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
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| Diastolic hypotension | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Respiratory rate increased | Investigations | MedDRA 18.0 | Systematic Assessment |
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| Bradycardia | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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At least 30 days prior to submission of communications, sponsor shall review and comment on the communications. Sponsor shall have the right to require institution and investigator to remove specifically identified confidential information and to delay the proposed publication an additional 45 days to enable sponsor to seek patent protection.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Trial Information | PAION UK Ltd | +49 2414453101 | reg_paion@paion.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 9, 2017 | Feb 15, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| C522201 | remimazolam |
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| ≥65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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