Antibiotics for Appendicitis

Overseen By Jessica Garcia Lopez

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Wake Forest University Health Sciences

Must not be taking: Steroids, Chemotherapy, Immunosuppressants, Antibiotics

Disqualifiers: Pregnancy, Heart failure, Sepsis, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1-4 days

400 Participants Needed

Trial Summary

What is the purpose of this trial?

To demonstrate the safety, efficacy, and feasibility of short-course post-operative antibiotic treatment for simple and complicated appendicitis

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are currently using antibiotics for other reasons, you cannot participate.

What data supports the effectiveness of the drug for treating appendicitis?

Research shows that antibiotics can be effective for treating uncomplicated appendicitis, with success rates ranging from 86% to 100% in some studies. However, the long-term outcomes and recurrence rates vary, and more research is needed to confirm these findings. ^{1 2 3 4 5}

Are antibiotics generally safe for humans?

Antibiotics are generally safe for humans, but they can cause side effects like rash, diarrhea, and rare serious complications. They may also affect the heart and cause issues like low blood pressure or changes in heart rate, especially in complex surgical cases. It's important to use them correctly to avoid unnecessary risks. ^{6 7 8 9 10}

How does the drug treatment for appendicitis differ from other treatments?

The use of antibiotics for appendicitis is unique because it offers a non-surgical option for treating uncomplicated cases, potentially avoiding surgery altogether. This approach is particularly beneficial for patients at high surgical risk, such as those with perforated appendicitis or localized abscesses, where antibiotics can manage the condition effectively. ^{3 11 12 13 14}

Research Team

Rafael Torres Fajardo, MD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

This trial is for adults over 18 who need an appendectomy and can consent to the study. They must have a way to be contacted post-surgery. It's not for prisoners, those with weakened immune systems, allergies to Bupivacaine, suspected sepsis, uncontrolled diabetes or heart failure, pregnant women, or anyone on antibiotics for other reasons.

Inclusion Criteria

I am 18 years old or older.

Willing and able to provide informed consent

I am scheduled for an appendectomy.

Exclusion Criteria

I am suspected to have a severe infection according to the Sepsis-3 criteria.

Prisoners

I am currently taking antibiotics for a condition other than cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive post-operative antibiotics based on the group assignment: restricted or liberal duration

1-4 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up at least 30 days post-appendectomy

4 weeks

1 visit (telephone or electronic medical record review)

Treatment Details

Interventions

• Antibiotic

Trial Overview The CASA RELAX trial is testing if short-course antibiotic treatment after surgery for simple and complicated appendicitis is safe and effective compared to longer treatments.

Participant Groups

Group I: Restricted Post-Operative Antibiotics Group Experimental Treatment 1 Intervention

Participants undergoing standard of care (SOC) with simple appendicitis will not receive post-operative antibiotics. Participants undergoing standard of care (SOC) with complicated (gangrenous or perforated) appendicitis will receive 24 hours of SOC post-operative antibiotics.

Group II: Restricted Duration of SOC Antibiotic Use Experimental Treatment 1 Intervention

Use of Standard of Care Antibiotics, type as determined by the clinician, will be restricted to none or 24 hours of post-operatively.

Group III: Liberal Duration of SOC Antibiotic Use Experimental Treatment 1 Intervention

Use of Standard of Care Antibiotics, type as determined by the clinician, will be permitted for 24 hours or 4 days of post-operatively.

Group IV: Liberal Post-Operative Antibiotics Group Active Control 1 Intervention

Participants undergoing standard of care (SOC) with simple appendicitis will receive 24 hours of post-operative antibiotics. Participants undergoing standard of care (SOC) with complicated (gangrenous or perforated) appendicitis will receive 4 days of SOC post-operative antibiotics.

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Findings from Research

A systematic review of four randomized trials involving 900 patients found that antibiotic therapy for uncomplicated acute appendicitis resulted in fewer complications (18%) compared to immediate appendectomy (25%), although the difference in severe complications like perforation was not significant.

After one year, 63% of patients treated with antibiotics were asymptomatic, but this was lower than the 97% success rate for those who underwent immediate appendectomy, suggesting that while antibiotics can be effective, appendectomy remains the preferred treatment for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic therapy for acute appendicitis in adults. Fewer immediate complications than with surgery, but more subsequent failures. [2018]

In a study of 530 patients with uncomplicated acute appendicitis, 39.1% of those treated with antibiotics alone experienced a recurrence of appendicitis within 5 years, indicating a significant late recurrence rate.

Patients who underwent appendectomy had a higher overall complication rate (24.4%) compared to those treated with antibiotics (6.5%), suggesting that antibiotic therapy may be a safer alternative for managing uncomplicated cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial. Salminen, P., Tuominen, R., Paajanen, H., et al.[2022]

Antibiotics are effective in treating acute appendicitis complicated by local peritonitis, with a success rate of 92.8% and a low recurrence rate of 8.9%, indicating they can be a viable alternative to surgery in these cases.

For uncomplicated acute appendicitis, the evidence from randomized controlled trials is insufficient due to methodological issues, making it unclear whether antibiotics can be reliably recommended as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Can acute appendicitis be treated by antibiotics and in what conditions?]. Vons, C.[2009]

Antibiotic treatment for selected patients with uncomplicated acute appendicitis showed a trend towards fewer complications compared to surgery, with 68% of patients successfully treated with antibiotics alone.

Despite the potential for antibiotics as a primary treatment, the study indicates that appendectomy remains the gold standard due to issues like patient crossover to surgery and selection bias in the trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic therapy versus appendectomy for acute appendicitis: a meta-analysis. Varadhan, KK., Humes, DJ., Neal, KR., et al.[2021]

In a study of 119 patients with uncomplicated appendicitis and appendiceal diameters ≤ 10 mm, only 7.6% required surgery after initial antibiotic treatment, indicating a relatively low treatment failure rate.

Over a median follow-up of 14 months, 12.7% of patients experienced a recurrence of appendicitis, suggesting that antibiotic therapy can be a safe and effective option for select patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The outcome of antibiotic therapy for uncomplicated appendicitis with diameters ≤ 10 mm. Park, HC., Kim, MJ., Lee, BH.[2018]

While antibiotics are generally safe and effective, this review emphasizes the importance of recognizing rare but potentially life-threatening complications that can arise from their use.

Common side effects like rash and diarrhea are well-known, but healthcare providers and patients should be aware of the less common, serious adverse effects associated with antibiotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unusual effects of common antibiotics. Ruiz, ME., Wortmann, GW.[2019]

A randomized clinical trial and subsequent experiments revealed that antibiotics can cause adverse cardiovascular effects, including hypotension, bradycardia, and tachycardia, particularly in complex surgical cases.

These findings suggest a need to reconsider the use and duration of antibiotic therapy in postoperative care, advocating for a 'minimal' approach to antibiotic use in emergency abdominal surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular adverse effects of antimicrobials in complex surgical cases. Kuenneke, M., Stinner, B., Celik, I., et al.[2007]

Antibiotics, while commonly used in surgery, can cause various side effects including pharmacologic issues like nephrotoxicity and immunologic problems such as allergic reactions.

To reduce adverse effects and errors in antibiotic use, it is recommended to limit the selection to about ten effective antibiotics tailored to local conditions, ensuring appropriate use and minimizing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug therapy of surgical infections. Limits and dangers]. Hau, T.[2006]

Antibiotic treatment commonly leads to diarrhea, with varying incidence rates depending on the type of antibiotic and its pharmacokinetic properties.

Diarrhea related to antibiotics can be caused by Clostridium difficile or may occur without a clear cause, highlighting the need for management guidelines for affected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic-associated diarrhea. Bartlett, JG.[2019]

Certain commonly used antibiotics can lead to serious side effects such as cardiovascular depression and respiratory difficulties, which are not due to allergic reactions but rather direct effects on physiological functions.

These adverse effects are more likely to occur in patients with severe health conditions, those who take higher doses, or when antibiotics are used alongside other strong medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute adverse effects of antibiotics. Adams, HR.[2018]

In a study of 100 children under 10 years with acute appendicitis, the use of antibiotics before surgery significantly reduced postoperative infection complications, with only 10% experiencing such issues.

Cefoxitin was the most effective antibiotic regimen, resulting in only 4% infection complications, while the combination of clindamycin and amikacin led to the highest complication rate of 20%, highlighting the importance of selecting appropriate antibiotic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study of appendicitis in children treated with four different antibiotic regimens. Gutiérrez, C., Vila, J., Garcia-Sala, C., et al.[2019]

A single preoperative dose of ceftriaxone was associated with a lower average cost of treatment (approximately $200) compared to the traditional antibiotic regimen (approximately $900).

Despite the higher cost of the traditional method, group A experienced more complications with three wound infections and one intraperitoneal abscess, while group B had only one wound infection, suggesting that ceftriaxone may not be as effective in preventing postoperative infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cost analysis: metronidazole-amikacin vs. preoperative monodose of ceftriaxone in appendicitis. Preliminary report]. Baeza-Herrera, C., Jaimes, G., Rico-Mejía, E., et al.[2018]

In a study of 150 patients undergoing appendectomy, the use of prophylactic antibiotics (cefazolin or clindamycin/tobramycin) did not significantly reduce the rate of postoperative wound infections, as only 4% of patients developed infections across all groups.

Wound contamination was observed in 33% of cases, but the similar infection rates among the antibiotic and control groups suggest that careful surgical techniques and protective measures are more effective than routine antibiotic prophylaxis in preventing infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prospective study on the prevention of wound infections after appendectomy for acute appendicitis]. Amgwerd, R., Biegger, P.[2013]

Antimicrobial agents are recommended as the initial treatment for uncomplicated appendicitis, but many studies have been biased by including patients with resolving appendicitis.

There is a need for randomized controlled trials to better identify patients with complicated appendicitis who require surgery and to evaluate the best use of antibiotics for those with uncomplicated cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating appendicitis with antibiotics. Brook, I.[2016]

References

1. France pubmed.ncbi.nlm.nih.gov

Antibiotic therapy for acute appendicitis in adults. Fewer immediate complications than with surgery, but more subsequent failures. [2018]

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

Five-Year Follow-up of Antibiotic Therapy for Uncomplicated Acute Appendicitis in the APPAC Randomized Clinical Trial. [2022]

3. France pubmed.ncbi.nlm.nih.gov

[Can acute appendicitis be treated by antibiotics and in what conditions?]. [2009]

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

Antibiotic therapy versus appendectomy for acute appendicitis: a meta-analysis. [2021]

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

The outcome of antibiotic therapy for uncomplicated appendicitis with diameters ≤ 10 mm. [2018]

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

Unusual effects of common antibiotics. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Cardiovascular adverse effects of antimicrobials in complex surgical cases. [2007]

8. Germany pubmed.ncbi.nlm.nih.gov

[Drug therapy of surgical infections. Limits and dangers]. [2006]

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

Antibiotic-associated diarrhea. [2019]

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

Acute adverse effects of antibiotics. [2018]

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

Study of appendicitis in children treated with four different antibiotic regimens. [2019]

12. Mexico pubmed.ncbi.nlm.nih.gov

[Cost analysis: metronidazole-amikacin vs. preoperative monodose of ceftriaxone in appendicitis. Preliminary report]. [2018]

13. Switzerland pubmed.ncbi.nlm.nih.gov

[Prospective study on the prevention of wound infections after appendectomy for acute appendicitis]. [2013]

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

Treating appendicitis with antibiotics. [2016]