Covid19, Appendicitis, Cholecystitis, Acute, Cholecystitis; Gallstone, Cholecystitis
Conditions
Brief summary
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
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.
Interventions
PROCEDUREOperative management
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.
PROCEDURENon-operative management
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.
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Participants will be informed regarding the treatment they receive at the time of randomization.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* COVID-19 confirmed positive by a microbiologic test. * Mild COVID-19 - no or mild pneumonia * EITHER 1. Uncomplicated acute appendicitis without a fecalith OR 2. 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. <!-- --> 1. Murphy's sign 2. RUQ mass/pain/tenderness B. Systemic signs of inflammation etc. <!-- --> 1. Fever 2. elevated CRP 3. 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: 1. Persistent dyspnea 2. Persistent respiratory frequency \>30/min 3. Persistent blood oxygen saturation \<93% 4. Partial pressure of arterial oxygen to fraction of inspired oxygen ratio \<300 5. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Pulmonary Complications | Up to 90 days | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Post-intervention ICU Admission | Up to 90 days | ICU admission following randomization |
| Mortality (All Cause) | Up to 90 days | Any death |
| Median Length of Hospital Stay | Up to 90 days | Cumulative and individual length of hospitalization(s) |
| Number of Emergency Room Visits/Readmission | Up to 90 days | — |
| Complications as Measured by the Clavien-Dindo Classification | Up to 90 days | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Failure for Non-operative Management | Up to 90 days | Patients randomized to non-operative management who require non-elective surgery to remove the affected organ |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Operative Management Treatment with surgery
Operative management: 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. | 1 |
| Non-operative Management Treatment with antibiotics
Non-operative management: 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. | 1 |
| Total | 2 |
Baseline characteristics
| Characteristic | Non-operative Management | Total | Operative Management |
|---|---|---|---|
| Age, Continuous | 72 Years | 52 Years | 32 Years |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 1 participants | 2 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
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
Time frame: Up to 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Operative Management | Number of Participants With Pulmonary Complications | 0 Participants |
| Non-operative Management | Number of Participants With Pulmonary Complications | 0 Participants |
Secondary
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
Time frame: Up to 90 days
Population: Subject in the Operative management did not develop any complications that met Clavien-Dindo classification
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Operative Management | Complications as Measured by the Clavien-Dindo Classification | 1 score on a scale |
Secondary
Median Length of Hospital Stay
Cumulative and individual length of hospitalization(s)
Time frame: Up to 90 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Operative Management | Median Length of Hospital Stay | 44 Hours |
| Non-operative Management | Median Length of Hospital Stay | 137 Hours |
Secondary
Mortality (All Cause)
Any death
Time frame: Up to 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Operative Management | Mortality (All Cause) | 0 Participants |
| Non-operative Management | Mortality (All Cause) | 0 Participants |
Secondary
Number of Emergency Room Visits/Readmission
Time frame: Up to 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Operative Management | Number of Emergency Room Visits/Readmission | 0 Participants |
| Non-operative Management | Number of Emergency Room Visits/Readmission | 0 Participants |
Secondary
Number of Participants With Post-intervention ICU Admission
ICU admission following randomization
Time frame: Up to 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Operative Management | Number of Participants With Post-intervention ICU Admission | 0 Participants |
| Non-operative Management | Number of Participants With Post-intervention ICU Admission | 0 Participants |
Other Pre-specified
Number of Participants With Treatment Failure for Non-operative Management
Patients randomized to non-operative management who require non-elective surgery to remove the affected organ
Time frame: Up to 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Operative Management | Number of Participants With Treatment Failure for Non-operative Management | 0 Participants |