Surgery vs Non-Operative Management for Appendicitis

Overseen By Kevin Schuster, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must not be taking: Antibiotics

Disqualifiers: Pregnancy, Septic shock, Dialysis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 60 days

180 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on antibiotics for more than 24 hours before enrollment, you cannot participate.

What data supports the effectiveness of the treatment for appendicitis?

Research shows that non-operative management, which includes treatments like antibiotics and drainage, can be effective for certain types of appendicitis, such as when there is an abscess. Studies indicate that this approach can lead to good outcomes, although it may be more costly than immediate surgery. ^{1 2 3 4 5}

Is surgery or non-surgical treatment for appendicitis safe?

Appendectomy (surgical removal of the appendix) is generally considered safe, with most complications being minor. Non-surgical management, like using antibiotics, is also supported as safe for uncomplicated cases of appendicitis. ^{6 7 8 9 10}

How does surgical treatment for appendicitis differ from non-operative management?

Surgical treatment for appendicitis, known as appendectomy, involves the physical removal of the appendix through surgery, which is a direct and immediate approach to resolving the condition. This differs from non-operative management, which typically involves using antibiotics to treat the inflammation without surgery, potentially avoiding the risks and recovery time associated with surgical procedures. ^{6 11 12 13 14}

What is the purpose of this trial?

The investigators aim to determine if early operative intervention is superior to non-operative management for adult patients with computerized tomography (CT)-proven complicated appendicitis with phlegmon or abscess.

Eligibility Criteria

Adults with a specific type of appendicitis shown on CT scans, which includes a perforation and an abscess or phlegmon over 2 cm. Not eligible if they've had major abdominal surgery, recent hospitalization, septic shock at admission, need mechanical ventilation or dialysis, are pregnant, have had certain treatments prior to the trial or have specific antibiotic allergies.

Inclusion Criteria

My appendicitis is severe with a rupture and infection shown on a CT scan.

Exclusion Criteria

Antibiotic therapy greater than 24 hours prior to considering for enrollment.

I have tried draining fluid before being assigned to a treatment group.

I am allergic to common antibiotics and need alternative treatments.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants choose between operative and non-operative management for appendicitis with abscess or phlegmon

60 days

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

12 months

Treatment Details

Interventions

• Drainage or antibiotics
• Operative management

Trial Overview The study is comparing two approaches for treating complicated appendicitis: one group will undergo surgery while the other will receive non-surgical treatment with drainage or antibiotics. The goal is to see which method is more effective.

Participant Groups

Group I: Surgery Experimental Treatment 1 Intervention

Patients who choose operations will have surgery performed to remove the appendix laparoscopically, through 3 or 4 small incisions. All patients in the operative group will receive standard perioperative antibiotics. They will also have the abscess(es) drained during the same surgery if there is one present. In some cases, the operation may be too difficult to perform laparoscopically, so an open appendectomy will be performed, involving a longer incision to remove the appendix. In some cases, both laparoscopic and open are performed. The surgeon may also choose to remove a section of the intestine with the appendix or perform additional procedures.

Group II: Non-operative management Active Control 1 Intervention

If a patient chooses non-operative management and if an abscess is present and amenable to percutaneous drainage this will be performed. If there is no abscess or it is not amenable to drainage antibiotics alone will be provided.

Operative management is already approved in United States, European Union for the following indications:

Approved in United States as Surgical intervention for:

• Acute uncomplicated appendicitis
• Complicated appendicitis with abscess or phlegmon

Approved in European Union as Surgical intervention for:

• Acute uncomplicated appendicitis
• Complicated appendicitis with abscess or phlegmon

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Findings from Research

In a study involving children aged 7-17 with simple appendicitis, initially nonoperative treatment was found to have similar outcomes to immediate appendectomy, with complication rates of 12% and 11% respectively.

The nonoperative approach allowed 3 out of 4 children to avoid surgery altogether, and those who did require an appendectomy did not experience any complications post-surgery, indicating a safe and effective alternative treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of initially nonoperative treatment for acute simple appendicitis in children. Gorter, RR., van der Lee, JH., Heijsters, FACJ., et al.[2019]

In a study of 82 children with appendicular masses, early surgical intervention (appendectomy at presentation) resulted in a significantly shorter hospital stay (4.8 days) compared to nonsurgical management followed by interval appendectomy (13.2 days).

Patients who underwent early surgery had a lower rate of complications, such as superficial wound infections (0% in the surgical group vs. 8% in the nonsurgical group), highlighting the safety and efficacy of early surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective evaluation of nonsurgical versus surgical management of appendiceal mass. Samuel, M., Hosie, G., Holmes, K.[2022]

In a study of 119 patients with appendiceal inflammatory mass, nonoperative management led to a high recurrence rate of 71%, with over half requiring further surgical or radiological intervention, highlighting its limitations.

In contrast, patients who underwent surgery had no recurrences and a complication rate of 17.6%, suggesting that operative management is more effective and safer for treating appendiceal inflammatory masses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to treat an appendiceal inflammatory mass: operatively or nonoperatively? Deelder, JD., Richir, MC., Schoorl, T., et al.[2021]

Non-operative management followed by interval appendectomy was successful in 76.6% of cases, leading to lower postoperative morbidity and reduced need for extended resection compared to immediate surgery.

While the initial surgical costs were lower for the interval strategy ($4512 vs $6888), the total medical costs were higher due to longer overall treatment ($9591 vs $6888), indicating a trade-off between immediate costs and comprehensive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superior outcomes (but at higher costs) of non-operative management with interval appendectomy over immediate surgery in appendicitis with abscess: Results from a large adult population cohort. Watanabe, R., Otsuji, A., Nakamura, Y., et al.[2021]

In a study of 101 adult patients with complicated appendicitis, nonoperative management was successful in 86.1% of cases, indicating it can be an effective initial treatment option.

Patients who failed nonoperative management experienced significantly longer hospital stays (11 days) compared to those who underwent immediate surgery (5 days), highlighting the potential risks of delaying surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complicated appendicitis: Immediate operation or trial of nonoperative management? Nimmagadda, N., Matsushima, K., Piccinini, A., et al.[2019]

A study analyzing 7,778 adult appendectomies found that preoperative imaging is standard practice, with 96.1% of patients receiving imaging, primarily CT scans, leading to a low negative appendectomy rate of 3.8%.

The majority of appendectomies were performed laparoscopically (97.4%), resulting in high rates of same-day discharge (87.3%) and very low 30-day mortality (0.04%) and complication rates (3.0% for any complications).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The contemporary appendectomy for acute uncomplicated appendicitis in adults. Childers, CP., Dworsky, JQ., Maggard-Gibbons, M., et al.[2020]

In a study of 231,678 patients with uncomplicated appendicitis, nonoperative management was found to be safe, with only 5.9% experiencing treatment failure and 4.4% recurrence over a median follow-up of more than 7 years.

There were no deaths linked to treatment failure or recurrence, and the risk of perforation after discharge was about 3%, suggesting that nonoperative management can be a viable alternative to surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of patients with nonsurgically managed uncomplicated appendicitis. McCutcheon, BA., Chang, DC., Marcus, LP., et al.[2021]

Complications from appendectomy are rare, occurring in only 0.2% of cases, indicating that the procedure is generally safe.

However, laparoscopic appendectomy was associated with a higher rate of severe complications compared to open surgery, leading to more cases requiring additional surgery or resulting in organ failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Complications of Laparoscopic and Conventional Appendectomy Reported to the Finnish Patient Insurance Centre. Kotaluoto, S., Pauniaho, SL., Helminen, MT., et al.[2018]

Early laparoscopic appendectomy (LA) for children with an appendiceal mass can be performed safely, with no perioperative or postoperative mortalities and minimal morbidity, indicating its safety as a treatment option.

While early LA for appendiceal mass resulted in longer operating times and recovery metrics compared to simple appendicitis, it is still a viable option that can prevent misdiagnoses and the need for additional hospital visits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is early laparoscopic appendectomy feasible in children with acute appendicitis presenting with an appendiceal mass? A prospective study. Goh, BK., Chui, CH., Yap, TL., et al.[2022]

In a study of 32 patients with appendiceal masses, those who received initial nonoperative treatment followed by interval laparoscopic appendectomy showed significant improvement and a quicker return to normal activities compared to those who underwent immediate surgery.

The safety and complication rates were comparable between the two groups, suggesting that interval laparoscopic appendectomy is a viable and effective alternative to immediate appendectomy for treating late appendicitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late-presenting appendicitis: a laparoscopic approach to a complicated problem. Gibeily, GJ., Ross, MN., Manning, DB., et al.[2018]

Recent evidence suggests a shift in clinical practice towards non-operative management of acute appendicitis, both in non-complicated and complicated cases, challenging the long-held belief that surgery is always necessary.

Despite appendectomy being the most common urgent surgical procedure for appendicitis, there is growing support for treating certain cases without surgery, indicating a potential change in how this condition is managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conservative treatment of acute appendicitis. Coccolini, F., Fugazzola, P., Sartelli, M., et al.[2023]

Nonoperative management of appendicitis is becoming more common, increasing from 3.6% in 2010 to 6.8% in 2014, but patients treated this way have a higher risk of readmission within 6 months compared to those who undergo surgery, with a 59% decreased odds of readmission for surgical patients.

Despite the higher risk of readmission, nonoperative management results in lower overall costs, with an adjusted cost increase of $2900 associated with surgical treatment, highlighting the need for careful patient assessment when considering treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Unintended Consequences of Nonoperative Management of Acute Appendicitis. Oliveira, K., Jean, RA., Gonsai, R., et al.[2020]

In a study of 190 children with suspected acute appendicitis, a non-operative management approach led to symptom resolution in 87.3% of patients, highlighting its efficacy as a treatment option for uncomplicated cases.

Factors such as shorter symptom duration (≤ 24 hours), lower white blood cell count (<12 × 10^9 cells/L), and smaller appendix size on ultrasound were associated with higher success rates for non-operative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of nonoperative treatment of acute appendicitis in children: a prospective cohort study. Perveen, S., Akhtar, J., Ali, S., et al.[2023]

In a review of five randomized controlled trials involving 1,430 adult patients, nonoperative treatment with antibiotics for uncomplicated acute appendicitis showed a significantly lower treatment efficacy (63.8%) compared to surgical management (93%).

However, the surgery group experienced a higher rate of complications (23.6%) compared to the antibiotics group (7.7%), suggesting that while surgery is more effective, it also carries greater risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Operation versus antibiotics--The "appendicitis conundrum" continues: A meta-analysis. Sakran, JV., Mylonas, KS., Gryparis, A., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Outcome of initially nonoperative treatment for acute simple appendicitis in children. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Prospective evaluation of nonsurgical versus surgical management of appendiceal mass. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

How to treat an appendiceal inflammatory mass: operatively or nonoperatively? [2021]

4. Japan pubmed.ncbi.nlm.nih.gov

Superior outcomes (but at higher costs) of non-operative management with interval appendectomy over immediate surgery in appendicitis with abscess: Results from a large adult population cohort. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Complicated appendicitis: Immediate operation or trial of nonoperative management? [2019]

6. United States pubmed.ncbi.nlm.nih.gov

The contemporary appendectomy for acute uncomplicated appendicitis in adults. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Long-term outcomes of patients with nonsurgically managed uncomplicated appendicitis. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Severe Complications of Laparoscopic and Conventional Appendectomy Reported to the Finnish Patient Insurance Centre. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Is early laparoscopic appendectomy feasible in children with acute appendicitis presenting with an appendiceal mass? A prospective study. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Late-presenting appendicitis: a laparoscopic approach to a complicated problem. [2018]

11. Italy pubmed.ncbi.nlm.nih.gov

Conservative treatment of acute appendicitis. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

The Unintended Consequences of Nonoperative Management of Acute Appendicitis. [2020]

13. India pubmed.ncbi.nlm.nih.gov

Feasibility of nonoperative treatment of acute appendicitis in children: a prospective cohort study. [2023]

14. United States pubmed.ncbi.nlm.nih.gov

Operation versus antibiotics--The "appendicitis conundrum" continues: A meta-analysis. [2022]