Operative vs Non-Operative Management of Acute Appendicitis and Acute Cholecystitis in COVID-19 Positive Patients

Study Overview
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Brief Summary
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This study evaluates operative and non-operative management of acute appendicitis (infection or inflammation of the appendix) and acute cholecystitis (inflammation/infection of the gallbladder) in patients with active mild to moderate COVID-19 infection. The hypothesis is that COVID+ patients with uncomplicated acute appendicitis or acute cholecystitis amendable to a laparoscopic procedure can have safe operative outcomes compared to those managed non-operatively.

Detailed Description
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As the novel coronavirus disease 2019 (COVID-19) disseminates across the United States, more routine preoperative testing is going to expose infected patients with no or mild pneumonia symptoms. Currently, little is known regarding the true consequences of general anesthesia in COVID-positive (COVID+) patients. Surgeons are going to face challenging decisions regarding whether or not to operate for non-elective cases requiring general anesthesia when non-operative treatment options exist. Patients with acute appendicitis are usually treated with an operation to remove the appendix, but they can also be initially treated with antibiotics and have an operation at a later date. Similarly, patients with acute cholecystitis are usually treated with an operation to remove the gallbladder, but they can be treated with antibiotics and a percutaneous cholecystostomy tube (a tube that going through the skin to drain the gallbladder) and have an operation at a later date. However, patients managed without a definitive operation may require more resource utilization, PPE consumption, interactions with hospital personnel, and could experience treatment failures that exacerbate their viral illness. This is a pilot study comparing the safety of operative versus non-operative management of COVID+ patients with mild to moderate symptoms.

Official Title
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Operative vs Non-Operative Management of Acute Appendicitis and Acute Cholecystitis in COVID-19 Positive Patients

Conditions
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Covid19, Appendicitis, Cholecystitis, Acute, Cholecystitis; Gallstone, Cholecystitis

Intervention / Treatment
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* Procedure: Operative management
* Procedure: Non-operative management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COVID-19 confirmed positive by a microbiologic test. Mild COVID-19 - no or mild pneumonia EITHER Uncomplicated acute appendicitis without a fecalith OR Acute cholecystitis - by TG18/TG13 diagnostic criteria where definite diagnosis requires one item in A + one item in B + C A. Local signs of inflammation etc. Murphy's sign RUQ mass/pain/tenderness B. Systemic signs of inflammation etc. Fever elevated CRP elevated WBC count C. Imaging findings characteristic of acute cholecystitis Exclusion Criteria: Active pregnancy COVID-19 severe disease that would be a contraindication to operative intervention at the discretion of the attending surgeon supported by the following, none of which are individually required or are a strict exclusion criterion as some of these could be attributed or exacerbated by the underlying surgical problem: Persistent dyspnea Persistent respiratory frequency >30/min Persistent blood oxygen saturation <93% Partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300 Lung infiltrates >50% COVID-19 critical disease - respiratory failure, shock, or multiorgan dysfunction The surgeon expects increased operative complexity - high risk of conversion to open or prolonged procedure Unable or unwilling to consent or fulfill study procedures - need to complete 90 day follow-up by telephone

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
Interventional Model Description: This will be a prospective, non-blinded, pilot randomized controlled trial comparing operative to non-operative management of acute appendicitis and acute cholecystitis in patients with mild to moderate COVID-19 infection. This will be a two-arm trial with intervention 1: intervention 2 allocation ratio of 1:1.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Operative management<br>Treatment with surgery | Procedure: Operative management<br>* Patients will undergo surgical removal of the affected organ. The initial approach will be in a minimally invasive, laparoscopic fashion. If necessary, conversion to an open operation may be performed. These patients will be treated preoperatively and postoperatively with similar antibiotic regimens, however the duration of antibiotic therapies will be dependent on factors such as intraoperative findings, resolution of laboratory abnormalities, and tolerance of oral medications.<br>|
| Active Comparator: Non-operative management<br>Treatment with antibiotics | Procedure: Non-operative management<br>* Patients will be treated with 3 days of intravenous antibiotics followed by 7 days of oral antibiotics, as described below: Non-penicillin allergic patients piperacillin/tazobactam 3.375g IV every 6 hours for 3 days amoxicillin/clavulanate 875/125mg by mouth every 12 hours for 7 days Penicillin allergic patients ertapenem 1g IV every 24 hours for 3 days ciprofloxacin 500mg every 12 hours AND metronidazole 500mg every 8 hours for 7 days Patients may be considered to have failed non-operative management (e.g. treatment failure) if they experience absence of clinical improvement, worsening abdominal pain and/or localized/diffuse peritonitis in the judgment of the treating surgeon at any point within the study window. If this occurs, then surgeons may proceed with rescue appendectomy or percutaneous drainage in the setting of appendicitis, or with placement of a percutaneous cholecystostomy tube in the setting of acute cholecystitis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Pulmonary Complications | Including pneumonia, acute respiratory distress syndrome (ARDS) or unexpected postoperative ventilation For operative management this means any episode of non-invasive ventilation, invasive ventilation, or extracorporeal membrane oxygenation after initial extubation after surgery, or patient cannot be extubated as planned after surgery. For non-operative management this means any intubation | Up to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Post-intervention ICU Admission | ICU admission following randomization | Up to 90 days | 
| Mortality (All Cause) | Any death | Up to 90 days | 
| Complications as Measured by the Clavien-Dindo Classification | The Clavien-Dindo classification is a grading scale from 1 to 5 (with 5 being more severe0 to objectively describe the severity of a complication, including any deviation from the normal postoperative course | Up to 90 days | 
| Median Length of Hospital Stay | Cumulative and individual length of hospitalization(s) | Up to 90 days | 
| Number of Emergency Room Visits/Readmission |  | Up to 90 days |