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| Name | Class |
|---|---|
| University of Utah | OTHER |
| Integra LifeSciences Corporation | INDUSTRY |
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The Placebo-Controlled Effectiveness in Idiopathic Normal Pressure Hydrocephalus (iNPH) Shunting (PENS) trial is a multi-center blinded, randomized, placebo-controlled design investigation of cerebrospinal fluid (CSF) shunt surgery to study the shunt effectiveness in iNPH patients.
The primary intervention will be setting the FDA-approved Certas Plus with Siphonguard, programmable CSF shunt valve to active (open shunt group)(setting 4)(110 mm H2O) or placebo (closed shunt group)(setting 8)(>400 mm H2O)in a 1:1 ratio. By the time of the primary objective evaluation at four months, the closed shunt group will have zero months of active treatment, and the open shunt group will have four months of active treatment. At four months, shunts for subjects in the closed shunt group will be adjusted to setting 4. To maintain blinding, all patients will be adjusted/ mock adjusted to the active setting in a similar fashion. Patients from both groups will not be adjusted before four months of active treatment, unless judged medically necessary by the treating team. Following four months of active treatment, all subjects in each group will have shunt adjustments according to clinical standards at each center.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open Shunt Group | Active Comparator | FDA-approved Certas Plus with Siphonguard, programmable CSF shunt valve setting to active (open shunt group)(setting 4)(110 mm H2O) at time of shunt implantation |
|
| Closed Shunt Group | Sham Comparator | FDA-approved Certas Plus with Siphonguard, programmable CSF shunt valve setting to placebo (closed shunt group)(setting 8)(>400 mm H2O) at time of shunt implantation followed by setting to active (setting 4) (110 mm H2O) four months after the procedure. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| programmable CSF shunt valve | Device | Brain shunt surgery using a programmable CSF shunt valve |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Gait Velocity | Evaluation of CSF shunting in Idiopathic Normal Pressure Hydrocephalus (INPH) patients through a group comparison of improvement from baseline at four months between active and placebo-controlled groups, using the primary endpoint of gait velocity in meters per second (m/s). | Baseline and 4 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Cognition as Assessed by the Montreal Cognitive Assessment (MoCA) Score | Evaluate the effect of shunting between active and placebo-controlled groups at four months using MoCA test to assess cognition. Scores on the MoCA range from 0 to 30 where lower scores signify greater cognitive impairment. | Baseline and 4 Months |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Function as Assessed by the Lawton Activities of Daily Living/Independence in Activities of Daily Living (ADL/IADL) Test Score | Evaluate the effect of shunting between active and placebo-controlled groups on change from baseline to four months using ADL/IADL test to assess function. Scores on the Lawton ADL/IADL scale range from 0 to 32 where a lower score indicates less independence in physical and instrumental daily living skills. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mark Luciano, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Medicine | Baltimore | Maryland | 21287 | United States | ||
| University of New Mexico |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36700738 | Derived | Luciano M, Holubkov R, Williams MA, Malm J, Nagel S, Moghekar A, Eklund A, Zwimpfer T, Katzen H, Hanley DF, Hamilton MG; PENS Co-investigators and AHCRN Site PIs. Placebo-Controlled Effectiveness of Idiopathic Normal Pressure Hydrocephalus Shunting: A Randomized Pilot Trial. Neurosurgery. 2023 Mar 1;92(3):481-489. doi: 10.1227/neu.0000000000002225. Epub 2022 Nov 25. |
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After subject enrollment and follow up have been completed, the Data Coordinating Center (DCC) of the study will prepare a final study database for analysis. A releasable database will be produced and completely de-identified in accordance with the definitions provided in the Health insurance Portability and Accountability Act (HIPAA). Namely, all identifiers specified in HIPAA will be re-coded in a manner that will make it impossible to deduce or impute the specific identity of any patient. The database will not contain any institutional identifiers.
The DCC will also prepare a data dictionary that provides a concise definition of every data element included in the database. If specific data elements have idiosyncrasies that might affect interpretation or analysis, this will be discussed in the dictionary document.
In accordance with policies determined by the investigators and funding sponsors, the releasable database will be provided to users in electronic form.
One year after publication of the results of the primary analysis.
individual participant data (IPD) will be made available to researchers submitting a request for data that includes an analytic plan approved by the Institutional Review Board (IRB) at their institution
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| ID | Title | Description |
|---|---|---|
| FG000 | Open Shunt Group | FDA-approved Certas Plus with Siphonguard, programmable cerebrospinal fluid (CSF) shunt valve setting to active (open shunt group)(setting 4)(110 mm H2O) at time of shunt implantation programmable CSF shunt valve: Brain shunt surgery using a programmable CSF shunt valve |
| FG001 | Closed Shunt Group | FDA-approved Certas Plus with Siphonguard, programmable CSF shunt valve setting to placebo (closed shunt group)(setting 8)(>400 mm H2O) at time of shunt implantation followed by setting to active (setting 4) (110 mm H2O) four months after the procedure. programmable CSF shunt valve: Brain shunt surgery using a programmable CSF shunt valve |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Open Shunt Group | FDA-approved Certas Plus with Siphonguard, programmable CSF shunt valve setting to active (open shunt group)(setting 4)(110 mm H2O) at time of shunt implantation programmable CSF shunt valve: Brain shunt surgery using a programmable CSF shunt valve |
| BG001 | Closed Shunt Group |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 in Gait Velocity | Evaluation of CSF shunting in Idiopathic Normal Pressure Hydrocephalus (INPH) patients through a group comparison of improvement from baseline at four months between active and placebo-controlled groups, using the primary endpoint of gait velocity in meters per second (m/s). | Randomized patients alive at Month 4 | Posted | Mean | Standard Deviation | meters per second | Baseline and 4 months |
|
From time of randomization until 1 year after initial shunting procedure.
There are two intervention groups in the study. Open shunt arm starts with shunt "active" at the time of shunt insertion. Closed shunt arm begins with an initial 4-month period where shunt is set to placebo and then to active after 4 months of shunt insertion. Adverse events were assessed for these two arms. Adverse events occurring during the period of the closed shunt were not separately monitored from adverse events occurring during the period of the open shunt for the Closed shunt group.
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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 | Open Shunt Group | FDA-approved Certas Plus with Siphonguard, programmable CSF shunt valve setting to active (open shunt group)(setting 4)(110 mm H2O) at time of shunt implantation programmable CSF shunt valve: Brain shunt surgery using a programmable CSF shunt valve |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Muscular Weakness | Musculoskeletal and connective tissue disorders | MedDRA (10.0) | Systematic Assessment | Hospitalization for Grade 3 Generalized Muscle Weakness |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Transient Decrease in MOCA Score | Investigations | MedDRA (10.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jessica Wollett | Johns Hopkins | 6673068141 | jwollet1@jh.edu |
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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 | May 8, 2020 | Mar 11, 2022 | Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 14, 2018 | Mar 11, 2022 | SAP_002.pdf |
| ICF | No | No | Yes | Informed Consent Form | Nov 21, 2019 | Mar 11, 2022 | ICF_003.pdf |
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The primary intervention will be the initiation of the randomized initial shunt valve opening pressure setting to create a delayed treatment group in half of the study patients.
Randomization will be to active or placebo (closed) shunt settings. At the time of the standard four-month evaluation, all subjects will be similarly non-invasively adjusted to bring all subjects in both groups to the active setting while maintaining blinding of the subjects. All settings will be verified by the adjusting neurosurgeon.
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| Change in Bladder Control as Assessed by the Overactive Bladder Questionnaire, Short Form |
Evaluate the effect of shunting between active and placebo-controlled groups at four months using Overactive Bladder Questionnaire, short form (OAB-q sf.) to assess bladder control. The OAB-q SF is scored from 0 to 100 with lower scores indicating worse QOL due to bladder control. |
| Baseline and 4 months |
| Baseline and 4 months |
| Change in Function as Assessed by the Modified Rankin Scale (MRS) | Evaluate the effect of shunting between active and placebo-controlled groups at four months using MRS to assess function. Scores on the MRS range from 0 to 6 where higher scores signify increased disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. | Baseline and 4 months |
| Change in Cognition as Assessed by the Symbol Digit Modalities Test (SDMT) | Evaluate the effect of shunting between active and placebo-controlled groups at four months using SDMT to assess cognition. Scores on the SDMT range from 0 to 110 where lower scores are associated with reduced psychomotor speed. | Baseline and 4 months |
| Change in Gait Velocity From Shunt Activation to 8 Months After Active Shunting | Evaluate the clinical improvement of all study participants at eight months of active shunting, using the primary outcome of gait velocity. For patients assigned to Open shunt, active shunting is from Baseline to Month 8 of the study. For patients assigned to Closed Shunt, active shunting is from Month 4 of the study (immediately prior to opening of initially Closed shunt) to Month 12 (i.e., after 8 months of the patient having an open shunt). | Up to 8 months after active shunting |
| Change in Cognition Using MoCA From Baseline to 8 Months After Active Shunting | Evaluate the clinical improvement of all study participants at eight months of active shunting using MoCA to assess cognition. Scores on the MoCA range from 0 to 30 where lower scores signify greater cognitive impairment. | Baseline and 8 months after active shunting |
| Change in Bladder Control From Baseline to 8 Months After Active Shunting | Evaluate the clinical improvement of all study participants at eight months of active shunting using OAB-q test to assess bladder control. The OAB-q SF is scored from 0 to 100 with lower scores indicating worse QOL due to bladder control. | Baseline and 8 months after active shunting |
| Change in Function Using ADL/IADL From Baseline to 8 Months After Active Shunting | Evaluate the effect of shunting between active and placebo-controlled groups on change from baseline to four months using ADL/IADL test to assess function. Scores on the Lawton ADL/IADL scale range from 0 to 32 where a lower score indicates less independence in physical and instrumental daily living skills. | Baseline and 8 months after active shunting |
| Change in Function Using MRS From Baseline to 8 Months After Active Shunting | Evaluate the effect of shunting between active and placebo-controlled groups at four months using MRS to assess function. Scores on the MRS range from 0 to 6 where higher scores signify increased disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. | Baseline and 8 months after active shunting |
| Change in Cognition Using SDMT From Baseline to 8 Months After Active Shunting | Evaluate the clinical improvement of all study participants at eight months of active shunting using SDMT to assess cognition. Scores on the SDMT range from 0 to 110 where lower scores are associated with reduced psychomotor speed. | Baseline and 8 months after active shunting |
| Number of Patients With Falls | Evaluate the effect of shunting between active and placebo-controlled groups at four months by assessing the number of patients with falls. | 4 months |
| Frequency of Adverse Effects | Evaluate the clinical improvement of all study participants at eight months of active shunting by assessing the frequency of falls, surgical and non-surgical complications, related and unrelated. | 8 months |
| Adverse Events | Compare adverse events (AEs) in the active versus placebo-controlled group at four months and at eight months of active shunting. | 4 and 8 months of active shunting |
| Albuquerque |
| New Mexico |
| 87106 |
| United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| University of Washington Medical Center | Seattle | Washington | 98196 | United States |
| University of Calgary | Calgary | Alberta | T2N 2T9 | Canada |
| Vancouver General Hospital/University of British Colombia | Vancouver | British Colombia | V5Z 1M9 | Canada |
| Umeå University | Umeå | Sweden |
FDA-approved Certas Plus with Siphonguard, programmable CSF shunt valve setting to placebo (closed shunt group)(setting 8)(>400 mm H2O) at time of shunt implantation followed by setting to active (setting 4) (110 mm H2O) four months after the procedure. programmable CSF shunt valve: Brain shunt surgery using a programmable CSF shunt valve |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| Evans' Ratio | Ratio (0-1) of the radiographic measure of the ventricular width of the largest frontal horn width (cm) and the greatest cerebral width in centimeters (cm) where a larger value indicates larger ventricular volume. The ratio has no unit. | Median | Inter-Quartile Range | no unit |
|
FDA-approved Certas Plus with Siphonguard, programmable CSF shunt valve setting to placebo (closed shunt group)(setting 8)(>400 mm H2O) at time of shunt implantation followed by setting to active (setting 4) (110 mm H2O) four months after the procedure. programmable CSF shunt valve: Brain shunt surgery using a programmable CSF shunt valve |
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| Secondary | Change in Cognition as Assessed by the Montreal Cognitive Assessment (MoCA) Score | Evaluate the effect of shunting between active and placebo-controlled groups at four months using MoCA test to assess cognition. Scores on the MoCA range from 0 to 30 where lower scores signify greater cognitive impairment. | Randomized patients alive at Month 4 | Posted | Mean | Standard Deviation | score on a scale | Baseline and 4 Months |
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| Secondary | Change in Bladder Control as Assessed by the Overactive Bladder Questionnaire, Short Form | Evaluate the effect of shunting between active and placebo-controlled groups at four months using Overactive Bladder Questionnaire, short form (OAB-q sf.) to assess bladder control. The OAB-q SF is scored from 0 to 100 with lower scores indicating worse QOL due to bladder control. | Randomized patients alive at Month 4 with Outcome Data at Baseline and Month 4. | Posted | Mean | Standard Deviation | score on a scale | Baseline and 4 months |
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| Other Pre-specified | Change in Function as Assessed by the Lawton Activities of Daily Living/Independence in Activities of Daily Living (ADL/IADL) Test Score | Evaluate the effect of shunting between active and placebo-controlled groups on change from baseline to four months using ADL/IADL test to assess function. Scores on the Lawton ADL/IADL scale range from 0 to 32 where a lower score indicates less independence in physical and instrumental daily living skills. | Randomized Patients alive at Month 4 with Outcome Data for both Baseline and Month 4. | Posted | Mean | Standard Deviation | score on a scale | Baseline and 4 months |
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| Other Pre-specified | Change in Function as Assessed by the Modified Rankin Scale (MRS) | Evaluate the effect of shunting between active and placebo-controlled groups at four months using MRS to assess function. Scores on the MRS range from 0 to 6 where higher scores signify increased disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. | Randomized Patients Alive at Month 4. | Posted | Mean | Standard Deviation | score on a scale | Baseline and 4 months |
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| Other Pre-specified | Change in Cognition as Assessed by the Symbol Digit Modalities Test (SDMT) | Evaluate the effect of shunting between active and placebo-controlled groups at four months using SDMT to assess cognition. Scores on the SDMT range from 0 to 110 where lower scores are associated with reduced psychomotor speed. | Randomized Patients Alive at Month 4. | Posted | Mean | Standard Deviation | score on a scale | Baseline and 4 months |
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| Other Pre-specified | Change in Gait Velocity From Shunt Activation to 8 Months After Active Shunting | Evaluate the clinical improvement of all study participants at eight months of active shunting, using the primary outcome of gait velocity. For patients assigned to Open shunt, active shunting is from Baseline to Month 8 of the study. For patients assigned to Closed Shunt, active shunting is from Month 4 of the study (immediately prior to opening of initially Closed shunt) to Month 12 (i.e., after 8 months of the patient having an open shunt). | All randomized patients alive with gait velocity evaluated 8 months after active shunting. | Posted | Mean | Standard Deviation | meters per second | Up to 8 months after active shunting |
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| Other Pre-specified | Change in Cognition Using MoCA From Baseline to 8 Months After Active Shunting | Evaluate the clinical improvement of all study participants at eight months of active shunting using MoCA to assess cognition. Scores on the MoCA range from 0 to 30 where lower scores signify greater cognitive impairment. | all patients with MoCA available at baseline and after 8 months of active shunting | Posted | Mean | Standard Deviation | score on a scale | Baseline and 8 months after active shunting |
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| Other Pre-specified | Change in Bladder Control From Baseline to 8 Months After Active Shunting | Evaluate the clinical improvement of all study participants at eight months of active shunting using OAB-q test to assess bladder control. The OAB-q SF is scored from 0 to 100 with lower scores indicating worse QOL due to bladder control. | Patients with outcome data available at baseline and at 8 months after active shunting | Posted | Mean | Standard Deviation | score on a scale | Baseline and 8 months after active shunting |
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| Other Pre-specified | Change in Function Using ADL/IADL From Baseline to 8 Months After Active Shunting | Evaluate the effect of shunting between active and placebo-controlled groups on change from baseline to four months using ADL/IADL test to assess function. Scores on the Lawton ADL/IADL scale range from 0 to 32 where a lower score indicates less independence in physical and instrumental daily living skills. | All participants with outcome data available at baseline and after 8 months of active shunting | Posted | Mean | Standard Deviation | score on a scale | Baseline and 8 months after active shunting |
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| Other Pre-specified | Change in Function Using MRS From Baseline to 8 Months After Active Shunting | Evaluate the effect of shunting between active and placebo-controlled groups at four months using MRS to assess function. Scores on the MRS range from 0 to 6 where higher scores signify increased disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. | All randomizred patients with MRS data at baseline and at 8 months of active shunting. | Posted | Mean | Standard Deviation | score on a scale | Baseline and 8 months after active shunting |
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| Other Pre-specified | Change in Cognition Using SDMT From Baseline to 8 Months After Active Shunting | Evaluate the clinical improvement of all study participants at eight months of active shunting using SDMT to assess cognition. Scores on the SDMT range from 0 to 110 where lower scores are associated with reduced psychomotor speed. | All patients with SDMT data available at baseline and 8 months after active shunting | Posted | Mean | Standard Deviation | score on a scale | Baseline and 8 months after active shunting |
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| Other Pre-specified | Number of Patients With Falls | Evaluate the effect of shunting between active and placebo-controlled groups at four months by assessing the number of patients with falls. | Posted | Count of Participants | Participants | 4 months |
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| Other Pre-specified | Frequency of Adverse Effects | Evaluate the clinical improvement of all study participants at eight months of active shunting by assessing the frequency of falls, surgical and non-surgical complications, related and unrelated. | Not Posted | 8 months | Participants |
| Other Pre-specified | Adverse Events | Compare adverse events (AEs) in the active versus placebo-controlled group at four months and at eight months of active shunting. | Not Posted | 4 and 8 months of active shunting | Participants |
| 1 |
| 9 |
| 3 |
| 9 |
| 6 |
| 9 |
| EG001 | Closed Shunt Group | FDA-approved Certas Plus with Siphonguard, programmable CSF shunt valve setting to placebo (closed shunt group)(setting 8)(>400 mm H2O) at time of shunt implantation followed by setting to active (setting 4) (110 mm H2O) four months after the procedure. programmable CSF shunt valve: Brain shunt surgery using a programmable CSF shunt valve | 1 | 9 | 1 | 9 | 4 | 9 |
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| Cerebrovascular Accident | Nervous system disorders | MedDRA (10.0) | Systematic Assessment | Stroke |
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| Urosepsis | Infections and infestations | MedDRA (10.0) | Systematic Assessment | Hospitalization for Septic urinary tract infection (UTI) |
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| Subdural Effusion | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
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| Coagulopathy | Blood and lymphatic system disorders | MedDRA (10.0) | Systematic Assessment |
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| Gallbladder necrosis | Hepatobiliary disorders | MedDRA (10.0) | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
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| Abdominal tenderness | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Head injury | Injury, poisoning and procedural complications | MedDRA (10.0) | Systematic Assessment | External head trauma |
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| Abdominal pain | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment | Abdominal cramping |
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| Dizziness | Nervous system disorders | MedDRA (10.0) | Systematic Assessment |
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| Balance disorder | Nervous system disorders | MedDRA (10.0) | Systematic Assessment | Residual balance issues |
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| Crohn's disease | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA (10.0) | Systematic Assessment | Fever of unknown origin |
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