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

Covid19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04748120
• Other study ID #: 20-525
• Status: Terminated
• Phase: N/A
• Start date: December 28, 2020
• Est. completion date: April 6, 2021

Study information

• Verified date: March 2022
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: April 6, 2021
• Est. primary completion date: April 6, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Appendicitis
• Cholecystitis
• Cholecystitis, Acute
• Cholecystitis; Gallstone
• COVID-19
• Covid19
• Gallstones

Intervention

Procedure:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Cleveland Clinic Foundation	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Country where clinical trial is conducted

United States, 

References & Publications (7)

Aminian A, Safari S, Razeghian-Jahromi A, Ghorbani M, Delaney CP. COVID-19 Outbreak and Surgical Practice: Unexpected Fatality in Perioperative Period. Ann Surg. 2020 Jul;272(1):e27-e29. doi: 10.1097/SLA.0000000000003925. — View Citation

Davis CA, Landercasper J, Gundersen LH, Lambert PJ. Effective use of percutaneous cholecystostomy in high-risk surgical patients: techniques, tube management, and results. Arch Surg. 1999 Jul;134(7):727-31; discussion 731-2. — View Citation

Gomi H, Solomkin JS, Schlossberg D, Okamoto K, Takada T, Strasberg SM, Ukai T, Endo I, Iwashita Y, Hibi T, Pitt HA, Matsunaga N, Takamori Y, Umezawa A, Asai K, Suzuki K, Han HS, Hwang TL, Mori Y, Yoon YS, Huang WS, Belli G, Dervenis C, Yokoe M, Kiriyama S, Itoi T, Jagannath P, Garden OJ, Miura F, de Santibañes E, Shikata S, Noguchi Y, Wada K, Honda G, Supe AN, Yoshida M, Mayumi T, Gouma DJ, Deziel DJ, Liau KH, Chen MF, Liu KH, Su CH, Chan ACW, Yoon DS, Choi IS, Jonas E, Chen XP, Fan ST, Ker CG, Giménez ME, Kitano S, Inomata M, Mukai S, Higuchi R, Hirata K, Inui K, Sumiyama Y, Yamamoto M. Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci. 2018 Jan;25(1):3-16. doi: 10.1002/jhbp.518. Epub 2018 Jan 9. Review. — View Citation

Lei S, Jiang F, Su W, Chen C, Chen J, Mei W, Zhan LY, Jia Y, Zhang L, Liu D, Xia ZY, Xia Z. Clinical characteristics and outcomes of patients undergoing surgeries during the incubation period of COVID-19 infection. EClinicalMedicine. 2020 Apr 5;21:100331. doi: 10.1016/j.eclinm.2020.100331. eCollection 2020 Apr. — View Citation

Podda M, Gerardi C, Cillara N, Fearnhead N, Gomes CA, Birindelli A, Mulliri A, Davies RJ, Di Saverio S. Antibiotic Treatment and Appendectomy for Uncomplicated Acute Appendicitis in Adults and Children: A Systematic Review and Meta-analysis. Ann Surg. 2019 Dec;270(6):1028-1040. doi: 10.1097/SLA.0000000000003225. — View Citation

Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. — View Citation

Yokoe M, Hata J, Takada T, Strasberg SM, Asbun HJ, Wakabayashi G, Kozaka K, Endo I, Deziel DJ, Miura F, Okamoto K, Hwang TL, Huang WS, Ker CG, Chen MF, Han HS, Yoon YS, Choi IS, Yoon DS, Noguchi Y, Shikata S, Ukai T, Higuchi R, Gabata T, Mori Y, Iwashita Y, Hibi T, Jagannath P, Jonas E, Liau KH, Dervenis C, Gouma DJ, Cherqui D, Belli G, Garden OJ, Giménez ME, de Santibañes E, Suzuki K, Umezawa A, Supe AN, Pitt HA, Singh H, Chan ACW, Lau WY, Teoh AYB, Honda G, Sugioka A, Asai K, Gomi H, Itoi T, Kiriyama S, Yoshida M, Mayumi T, Matsumura N, Tokumura H, Kitano S, Hirata K, Inui K, Sumiyama Y, Yamamoto M. Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholecystitis (with videos). J Hepatobiliary Pancreat Sci. 2018 Jan;25(1):41-54. doi: 10.1002/jhbp.515. Epub 2018 Jan 9. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	Up to 90 days
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	Up to 90 days
Secondary	Number of Participants With Post-intervention ICU Admission	ICU admission following randomization	Up to 90 days
Secondary	Mortality (All Cause)	Any death	Up to 90 days
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	Up to 90 days
Secondary	Median Length of Hospital Stay	Cumulative and individual length of hospitalization(s)	Up to 90 days
Secondary	Number of Emergency Room Visits/Readmission		Up to 90 days