Antibiotics for Appendicitis

(CASA RELAX Trial)

Overseen By Brenda Nunez-Garcia

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Francisco

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

Disqualifiers: Pregnancy, Immunocompromised, Heart failure, Sepsis, Diabetes, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1-4 days

145 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to use antibiotics after appendicitis surgery. Researchers compare two approaches: a shorter antibiotic treatment and a longer course, to determine which is safer and more effective. The trial includes individuals who have undergone appendicitis surgery, covering both simple and complicated cases. Ideal participants are those who have recently had an appendectomy (surgery to remove the appendix) and can be easily contacted after hospital discharge. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those currently using antibiotics for other reasons. It's best to discuss your specific medications with the trial team.

What is the safety track record for these treatments?

Research shows that antibiotics are generally safe for treating appendicitis. Studies have found that antibiotics can be as effective as surgery for simple cases, indicating that the body usually tolerates antibiotics well in these situations.

For more complicated appendicitis, research indicates that antibiotics are often used after surgery. However, some issues can arise. Certain studies found higher rates of hospital readmissions and cases of abdominal abscesses (an infection that creates a pocket of pus) when specific antibiotics were used. This suggests that while antibiotics are generally safe, they might not be effective in every case.

Overall, antibiotics for appendicitis have been widely used and are considered a standard treatment option. Although there are some risks, especially for complicated cases, they are usually well-tolerated. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it explores how varying durations of post-operative antibiotic use can affect recovery from appendicitis. Unlike the traditional approach where antibiotics are used liberally after surgery, the trial compares a restricted use strategy, potentially reducing medication exposure. This could not only lessen side effects and antibiotic resistance but also streamline care for patients with simple appendicitis. By examining both simple and complicated cases, researchers aim to refine and optimize antibiotic use, which could lead to more personalized and effective treatment plans.

What evidence suggests that this trial's treatments could be effective for appendicitis?

Research has shown that antibiotics effectively treat appendicitis, especially after surgery. In this trial, participants will be divided into two groups to evaluate different post-operative antibiotic strategies. The Restricted Post-Operative Antibiotics Group will not receive antibiotics after surgery for simple appendicitis but will receive up to 24 hours of antibiotics for complicated cases. The Liberal Post-Operative Antibiotics Group will receive 24 hours of antibiotics for simple appendicitis and 4 days for complicated cases. Studies have found that antibiotics after surgery can help prevent infections, particularly in more serious cases like when the appendix bursts, where antibiotics are crucial for recovery. Patients with less severe appendicitis might not always need antibiotics after surgery, so treatment can differ based on the severity of the condition. The effectiveness of antibiotics for appendicitis is well-proven, which is why they are commonly used in standard care.

Who Is on the Research Team?

Lucy Kornblith, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Adults over 18 with appendicitis who are undergoing an appendectomy and can be contacted post-surgery. Excluded are those with Type 1 Diabetes or uncontrolled sugar levels, immune system issues due to medications or conditions like AIDS, allergies to bupivacaine, heart failure, suspected sepsis, current antibiotic use for other reasons, or if they're unlikely to follow the study plan.

Inclusion Criteria

I am scheduled for an appendectomy.

I have a working phone or reliable way to be contacted after leaving the hospital.

Exclusion Criteria

My surgeon has a preferred method for my surgery.

Research team unavailable

Prisoners

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive post-operative antibiotics based on the type of appendicitis: up to 24 hours for complicated cases in the restricted group, and 24 hours to 4 days in the liberal group

1-4 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on infectious/antibiotic complications and mortality

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Multiple standard of care antibiotics for appendicitis

Trial Overview The trial is testing whether a short course of various standard antibiotics after surgery is safe and effective for treating simple and complicated appendicitis. The exact antibiotics used are chosen by the doctors involved in the case.

How Is the Trial Designed?

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 with complicated (gangrenous or perforated) appendicitis will receive up to 24 hours of SOC post-operative antibiotics.

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

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

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

In a study of 288 children with acute appendicitis, both cefoxitin and ceftizoxime showed similar clinical responses and rates of infectious complications, indicating that both antibiotics are effective treatments.

Ceftizoxime, with its longer half-life, offers a practical advantage over cefoxitin, making it a suitable alternative for treating acute appendicitis in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prospective and comparative study of cefoxitin and ceftizoxime in appendicitis surgery]. Sanz Villa, N., Alvarez Bernaldo de Quirós, M., Cortés Gómez, MJ., et al.[2013]

In a randomized trial involving 73 children undergoing appendectomy, the combination of sulbactam and ampicillin was found to be at least as effective as metronidazole and cefotaxime in preventing infections after surgery, with fewer wound infections reported in the sulbactam group (3 vs. 5).

Sulbactam, as a beta-lactamase inhibitor, enhances the effectiveness of ampicillin, making it a suitable and well-tolerated prophylactic option for preventing sepsis in acute appendicitis cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized comparative study of sulbactam plus ampicillin vs. metronidazole plus cefotaxime in the management of acute appendicitis in children. Foster, MC., Kapila, L., Morris, DL., et al.[2019]

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]

In a study of 98 patients who underwent appendectomy for complicated acute appendicitis, carbapenems were found to be more effective than ciprofloxacin/metronidazole, with fewer cases requiring antibiotic rotation (14.3% vs. 0%; p = 0.004).

Patients treated with carbapenems had a significantly shorter hospital stay (4.45 days) compared to those on ciprofloxacin/metronidazole (8.29 days; p = 0.020) and experienced a higher rate of curative resolution (35/49 vs. 15/49; p < 0.001).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carbapenems versus ciprofloxacin/metronidazole for decreasing complications and hospital stay following complicated acute appendicitis surgery: A prospective cohort in an Ecuadorian population. Bunces-Orellana, O., Arevalo-Vidal, E., Bustos-Galarza, K., et al.[2022]

In a study of 864 patients undergoing appendectomy, a single dose of antibiotics resulted in a low rate of post-surgery septic complications (about 3%), with no significant difference among cefotaxime, cefoperazone, and moxalactam for early cases.

For late cases of appendicitis, moxalactam significantly reduced septic complications compared to the other antibiotics, proving to be safe and easier to administer, although its higher cost should be weighed against the benefits of reduced nursing time and monitoring needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, prospective, and double-blind trial of new beta-lactams in the treatment of appendicitis. Lau, WY., Fan, ST., Chu, KW., et al.[2021]

In a study of 209 patients with perforated or ruptured appendicitis, both cefoxitin and ampicillin + metronidazole resulted in wound infection rates of less than 10%, showing similar effectiveness in this regard.

However, cefoxitin was significantly more effective than ampicillin + metronidazole in preventing intra-abdominal abscesses, indicating that cefoxitin is a superior single-drug option for reducing postoperative infections in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Danish multicenter study: cefoxitin versus ampicillin + metronidazole in perforated appendicitis. [2019]

Switching from a triple antibiotic regimen to a single agent (amoxycillin/clavulanic acid) for treating complicated appendicitis resulted in a higher rate of surgical site infections (22.7% vs. 13.3%), indicating potential safety concerns with the single-agent approach.

Despite the increased rate of surgical site infections with the single agent, overall morbidity measures such as ICU admissions, relook surgery rates, and length of hospital stay were similar between the two antibiotic protocols, suggesting that further research is needed to evaluate the cost-effectiveness and clinical outcomes of single-agent therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amoxycillin/Clavulanic acid monotherapy in complicated paediatric appendicitis: Good enough? van Coller, R., Arnold, M., le Roux, H., et al.[2022]

In a study of 90 patients with perforated appendicitis, the combination of systemic metronidazole and local ampicillin significantly reduced the incidence of wound infections compared to local ampicillin alone.

Despite no overall difference in postoperative septic complications or hospitalization time between the two treatment groups, the use of systemic metronidazole is recommended for better wound infection outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Septic complications after appendicectomy for perforated appendicitis. A controlled clinical trial metronidazole and topical ampicillin. Schultz, A., Jørgensen, PM., Jørgensen, SP.[2013]

Antimicrobial prophylaxis is recommended for all operations involving acute appendicitis, showing significant reductions in postoperative infections, especially in cases of perforated or gangrenous appendicitis, but also in nonperforated cases.

In elective colorectal surgeries, prophylactic antibiotics are essential, with a common regimen being oral neomycin/erythromycin combined with a short course of a systemic cephalosporin, particularly for patients with risk factors like prolonged surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antimicrobial prophylaxis for appendectomy and colorectal surgery. Gorbach, SL.[2019]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6502196/

Conservative treatment of acute appendicitis - PMC The primary outcomes were 1-Short-term efficacy of antibiotic treatment evaluated as failure of non-operative management with 7 days of amoxicillin and ...

2. idmp.ucsf.edu idmp.ucsf.edu/sites/g/files/tkssra4251/f/Ped_Appendicitis_Algorithm_SF_FINAL.pdf

Pediatric Appendicitis Clinical Algorithm Single daily dosing of ceftriaxone and metronidazole is as safe and effective as ampicillin, gentamicin and metronidazole for non-operative management of ...

3. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2320315

Antibiotic Therapy vs Appendectomy for Treatment of ... An increasing amount of evidence supports the use of antibiotics instead of surgery for treating patients with uncomplicated acute appendicitis.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8734493/

Oral Antibiotics for Uncomplicated Acute Appendicitis The World Society of Emergency Surgery 2020 guidelines recommend antibiotics as an effective and safe alternative to appendectomy for managing patients with ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022346823001483

Postoperative Antibiotics for Complicated Appendicitis in ... Postoperative use of PT for complicated appendicitis is associated with higher rates of readmissions and intraabdominal abscess when compared to CM.