Post-Operative Dosing of Dexamethasone in Patients With Brain Tumors After a Craniotomy, PODS Trial

Study Overview
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Brief Summary
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This phase II trial tests the effect of decreasing (tapering) doses of dexamethasone on steroid side effects in patients after surgery to remove (craniotomy) a brain tumor. Steroids are the gold standard post-surgery treatment to reduce swelling (edema) at the surgical site to reduce neurological symptoms. Although, corticosteroids reduce edema, they have side effects including high blood sugar, high blood pressure, and can impair wound healing. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response. It also works to treat other conditions by reducing swelling and redness. Tapering doses dexamethasone may decrease steroid side effects without increasing the risk of edema in patients with brain tumors after a craniotomy.

Detailed Description
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PRIMARY OBJECTIVES: I. The primary objective of this study is to evaluate the efficacy of a reduced dosage steroid schedule (RDS) in patients who have undergone craniotomy for high grade glioma (HGG), low grade glioma (LGG), brain metastasis (BM), and meningiomas as compared with the normal dosing schedule (NDS). II. RDS after undergoing craniotomy for brain tumor has no impact on length of stay, 30 day readmission, and need for repeat imaging when compared to NDS. SECONDARY OBJECTIVE: I. RDS after craniotomy for brain tumor has no impact on development of steroid related side effects (new onset or worsening hypertension, hyperglycemia, wound infection, impaired wound healing, steroid dependence, neuropsychiatric disturbance) when compared to NDS. TERTIARY/EXPLORATORY OBJECTIVE: I. RDS after craniotomy has no effect on lymphocyte count and differential at 10-14 days after surgery. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I (NDS): Patients receive tapering doses of dexamethasone on days 1-15. Patients also undergo blood sample collection at time of surgery, at follow up visits and optionally at wound check visit 10-14 days post operative at investigator availability. Patients additionally undergo magnetic resonance imaging (MRI) and computed tomography (CT) scan during inpatient stay as part of standard of care. ARM II (RDS): Patients receive tapering doses of dexamethasone on days 1-4. Patients may receive dexamethasone intravenously (IV) and restart the taper if clinically indicated. Patients also undergo blood sample collection at time of surgery, follow up visits and optionally at wound check visit 10-14 days post operative at investigator availability. Patients additionally undergo MRI and CT scan during inpatient stay as part of standard of care.

Official Title
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Post-Operative Dosing of Steroids Post Craniotomy for Brain Tumor (PODS)

Conditions
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Low Grade Glioma, Malignant Brain Glioma, Malignant Brain Neoplasm, Meningioma

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Procedure: Computed Tomography
* Drug: Dexamethasone
* Procedure: Magnetic Resonance Imaging
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with radiographic findings consistent with either HGG, LGG, Meningioma, or brain metastasis Age equal to or above 18 Exclusion Criteria: Known hypothalamic-pituitary-adrenal (HPA) axis dysfunction Tumor causing compression of the sella or pituitary dysfunction Known immunodeficiency - including but not limited to severe combined immunodeficiency (SCID), common variable immunodeficiency (CVID), lymphocytopenia Taking immunosuppressive drugs - including but not limited to methotrexate, mycophenolate, rapamycin, tacrolimus, adalimumab, infliximab. Greater than two weeks of recent daily corticosteroid use or the use of corticosteroids equivalent to > 85 mg of dexamethasone in the last month Current lymphoma or leukemia History of solid organ transplant Minors < 18 Pregnant women History of cerebrovascular accident leading to neurologic deficit

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (NDS)<br>Patients receive tapering doses of dexamethasone on days 1-15. Patients also undergo blood sample collection at time of surgery, at follow up visits and optionally at wound check visit 10-14 days post operative at investigator availability. Patients additionally undergo MRI and CT scan during inpatient stay as part of standard of care. | Procedure: Biospecimen Collection<br>* Undergo blood sample collection<br>* Other names: Specimen Collection;Procedure: Computed Tomography<br>* Undergo CT scan<br>* Other names: tomography;Drug: Dexamethasone<br>* Given dexamethasone or IV<br>* Other names: ZoDex;Procedure: Magnetic Resonance Imaging<br>* Undergo MRI<br>* Other names: Nuclear Magnetic Resonance Imaging;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Arm II (RDS)<br>Patients receive tapering doses of dexamethasone on days 1-4. Patients may receive dexamethasone IV and restart the taper if clinically indicated. Patients also undergo blood sample collection at time of surgery, follow up visits and optionally at wound check visit 10-14 days post operative at investigator availability. Patients additionally undergo MRI and CT scan during inpatient stay as part of standard of care. | Procedure: Biospecimen Collection<br>* Undergo blood sample collection<br>* Other names: Specimen Collection;Procedure: Computed Tomography<br>* Undergo CT scan<br>* Other names: tomography;Drug: Dexamethasone<br>* Given dexamethasone or IV<br>* Other names: ZoDex;Procedure: Magnetic Resonance Imaging<br>* Undergo MRI<br>* Other names: Nuclear Magnetic Resonance Imaging;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospital stay | The two-sample t-test or Mann-Whitney U test utilized to estimate the differences between the two groups. General linear model employed in the multivariable analysis to estimate the adjusted difference in length of hospital stay between the two groups after adjusting for other factors. | Up to 3 months | 
| 30-day repeat admission rate | Comparison between the two groups assessed using Fisher exact test or Chi-Square test. Logistic regression used to compare between the two groups after adjusting for other factors. Odds ratios (OR) and 95% confidence intervals (CIs) calculated to evaluate the strength of any association. | At 30 days after surgery | 
| Need for repeat head imaging | Comparison between the two groups assessed using Fisher exact test or Chi-Square test. Logistic regression used to compare between the two groups after adjusting for other factors. OR and 95% CIs calculated to evaluate the strength of any association. | Up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of new neurologic deficit | Comparison between the two groups assessed using Fisher exact test or Chi-Square test. Logistic regression used to compare between the two groups after adjusting for other factors. OR and 95% CIs calculated to evaluate the strength of any association. | At less than 30 days and at 3 months | 
| Breakthrough seizures | Comparison between the two groups assessed using Fisher exact test or Chi-Square test. Logistic regression used to compare between the two groups after adjusting for other factors. OR and 95% CIs calculated to evaluate the strength of any association. | Up to 30 days after surgery | 
| Evidence of Worsening Cerebral Edema | This measure will be a three-level scale determined by the final neuroradiology read of comparison imaging as either improved cerebral edema, stable cerebral edema, or worsened cerebral edema when evaluated on repeat CT Head without contrast. | Between 5 and 30 days after surgery | 
| Evaluation for Steroid Dependence | This measure will be evaluated in a binary manner as either the patient having been successfully weaned off of all steroids or the patient remaining on supplemental daily steroids due to the inability to wean off of steroids due to symptomatic adrenal insufficiency. The assessment of adrenal insufficiency will not be done as part of this the study, this study will document the continued use of supplemental daily steroids at 3 month follow-up versus not. | At long term follow up to 3 months after surgery | 
| Rate of new onset hypertension | Defined as sustained systolic blood pressure > 140. Comparison between the two groups assessed using Fisher exact test or Chi-Square test. Logistic regression used to compare between the two groups after adjusting for other factors. OR and 95% CIs calculated to evaluate the strength of any association. | During inpatient stay up to 3 months after surgery | 
| Rate of new onset hyperglycemia | Defined as random blood glucose > 100 and/or new insulin requirement. Comparison between the two groups assessed using Fisher exact test or Chi-Square test. Logistic regression used to compare between the two groups after adjusting for other factors. OR and 95% CIs calculated to evaluate the strength of any association. | During inpatient stay up to 3 months after surgery | 
| Evaluation for Wound infection or Delayed Wound Healing | This criterion will be assessed via the Wound Check Form which uses a scale from 1-9 with worsening wound healing and infection indicated by an increased score. Modifiers A and B indicating cellulitis and purulence respectively are also added to the scale. The worst score on this scale would therefore be a 9AB, and a perfectly healed wound would be score of 1. | At 2 week wound check after surgery | 
| Evaluation for Need for Psychiatric Consult or Neuropsychiatric Side Effects | This criterion will be initially assessed via EPIC documentation via daily assessment via Neurosurgery residents whether the patient has experienced severe new onset behavioral issues in the post-op period typically associated with steroids (agitation, psychosis, mania). This will be then categorized into a binary system determining either the presence or absence of new severe agitation, psychosis, or mania. In addition, at the post operative visit, the patient will fill out the 'Dexamethasone Symptom questionnaire' which is a standardized questionnaire recording binary presence vs no presence of a list of common subjective symptoms experienced by patients on chronic steroids (headache, changes in body habitus etc) which will additionally be recorded. | At 2 week follow up after surgery | 
| Change in lymphocyte count and differential | Compared using the two-sample t-test. A general linear model will be used in the multivariable analysis to estimate the adjusted difference. | At baseline and 10-14 days post-operative |