Antibiotic Duration for Appendicitis

(CASA-RELAX Trial)

Recruiting at 1 trial location

Overseen By Nick G Nash

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Louisville

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)

Compensation: Varies

Number of Visits: 2

Duration: 1-4 days

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This prospective trial will randomize patients who have had an appendectomy to two different durations of antibiotic therapy depending on the status of the appendicitis. For simple appendicitis, patients will be randomized to peri-operative antibiotics or 24 hours duration. For complex appendicitis, patients will be randomized to 24 hours or 4 days duration. Data will be collected prospectively and test the hypothesis that shorter durations of antibiotics will be non-inferior to the longer durations.

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 data supports the effectiveness of the drug for treating appendicitis?

Research shows that antibiotics can be effective in treating appendicitis, especially when it's complicated by local peritonitis (inflammation of the abdominal lining), with a success rate of 92.8%. However, for uncomplicated cases, the effectiveness varies, and the studies have limitations, making it hard to draw firm conclusions. ^{1 2 3 4 5}

Is antibiotic treatment for appendicitis safe for humans?

Antibiotic treatment for appendicitis is generally considered safe, with studies showing it can be a safe alternative to surgery for appendicitis, including during pregnancy. ^{6 7 8 9 10}

How does the antibiotic duration treatment for appendicitis differ from other treatments?

This treatment is unique because it explores the effectiveness of a shorter course of antibiotics (2-3 days) after surgery for complicated appendicitis, compared to the traditional longer duration (5-7 days). This approach aims to reduce the risk of antibiotic resistance and minimize side effects while maintaining effectiveness in preventing infections. ^{1 10 11 12 13}

Eligibility Criteria

This trial is for adults (18+) who are about to have their appendix removed due to appendicitis and can give informed consent. They must have a reliable way to be contacted after leaving the hospital.

Inclusion Criteria

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

Willing and able to provide informed consent

I am 18 years old or older.

Exclusion Criteria

I have heart failure.

I have Type 1 Diabetes or my blood sugar levels are very high and hard to control.

I am hospitalized for appendicitis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants are randomized to receive either restrictive or liberal post-operative antibiotic therapy based on the complexity of appendicitis

1-4 days

In-hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, with data collected through medical records and a telephone call

4 weeks

1 call (telephone)

Treatment Details

Interventions

• Antibiotic
• Antibiotics

Trial Overview The study is testing if shorter antibiotic treatments work just as well as longer ones after appendix surgery. Patients with simple appendicitis will get either peri-operative antibiotics or a 24-hour dose, while those with complex cases will receive either a 24-hour or a four-day course.

Participant Groups

Group I: under 65 years simple appendicitis restricted duration Active Control 1 Intervention

simple appendicitis restricted duration of no postop antibiotics

Group II: Over 65 complex appendicitis restricted antibiotic duration Active Control 1 Intervention

see above for under 65

Group III: Under 65 simple appendicitis liberal duration Active Control 1 Intervention

simple appendicitis liberal duration of 24 hours postop antibiotics

Group IV: Under 65 complex appendicitis restricted duration Active Control 1 Intervention

complex appendicitis restricted duration of 24 hours postop antibiotics

Group V: Under 65 complex appendicitis liberal duration Active Control 1 Intervention

complex appendicitis liberal duration of 4 days of postop antibiotics

Group VI: Over 65 simple appendicitis restricted antibiotic duration Active Control 1 Intervention

see above for under 65

Group VII: Over 65 simple appendicitis liberal antibiotic duration Active Control 1 Intervention

see above for under 65

Group VIII: Over 65 appendicitis liberal antibiotic duration Active Control 1 Intervention

see above for under 65

Who Is Running the Clinical Trial?

University of Louisville

Lead Sponsor

Trials

353

Recruited

76,400+

Findings from Research

In a study of 1975 patients undergoing laparoscopic appendectomy for acute complicated appendicitis, extending antibiotic treatment from 3 days to 5 days did not significantly reduce the risk of infectious complications or intra-abdominal abscesses.

The only independent risk factor for developing infectious complications was the perforation of the appendix, suggesting that shorter antibiotic courses may be safe for nonperforated complicated appendicitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic Duration After Laparoscopic Appendectomy for Acute Complicated Appendicitis. van Rossem, CC., Schreinemacher, MH., van Geloven, AA., et al.[2016]

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 1143 patients who underwent appendicectomy for acute appendicitis, 3 days of postoperative antibiotic treatment was found to be as effective as 5 days in preventing infections, such as intra-abdominal abscesses and wound infections.

The study suggests that shorter antibiotic courses may be sufficient for patients with complicated appendicitis, potentially reducing unnecessary medication exposure without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duration of antibiotic treatment after appendicectomy for acute complicated appendicitis. van Rossem, CC., Schreinemacher, MH., Treskes, K., et al.[2022]

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]

In a study involving patients with acute appendicitis, adding a 7-day course of oral antibiotics after intravenous antibiotics did not significantly reduce postoperative infectious complications, with rates of 11.5% in the placebo group and 12.1% in the oral antibiotics group.

The study monitored patients for a minimum of 3 months post-appendectomy, indicating that the addition of oral antibiotics may not provide additional safety or efficacy in preventing infections after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of postoperative oral antibiotics in appendicitis: a randomized prospective double-blinded study. Taylor, E., Berjis, A., Bosch, T., et al.[2013]

Antibiotics for treating appendicitis are safe and can be as effective as surgery, with 21% of patients who started antibiotics undergoing appendectomy within 30 days, highlighting the need for personalized treatment decisions.

Factors such as female sex, a wider appendiceal diameter, and the presence of an appendicolith significantly increased the likelihood of needing surgery within 30 days, while traditional indicators of appendicitis severity did not correlate with this outcome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Factors Associated With Appendectomy Within 30 Days of Initiating Antibiotic Treatment for Appendicitis. Monsell, SE., Voldal, EC., Davidson, GH., et al.[2023]

Antibiotic treatment for acute appendicitis is a safe and effective first-line therapy, with a long-term relapse rate of about 15% after an initial favorable response, based on a study of 710 patients followed for nearly 6 years.

The cumulative probability of requiring surgery for relapse was low, with only 9% to 13% of patients needing an appendectomy within 5 years, suggesting that antibiotics can significantly reduce the need for surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Results Following Antibiotic Treatment of Acute Appendicitis in Adults. Lundholm, K., Hansson-Assarsson, J., Engström, C., et al.[2022]

A 6-year study involving 20 pregnant women with uncomplicated appendicitis showed that a 4-day course of antibiotics can be a feasible treatment option, with a treatment failure rate of 25%.

Despite some treatment failures, there were no severe maternal or fetal complications reported, suggesting that antibiotic therapy may be a safe alternative to surgery in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Antibiotic Therapy for Uncomplicated Appendicitis in Pregnancy. Joo, JI., Park, HC., Kim, MJ., et al.[2018]

A 7-day course of intravenous antibiotics (amoxicillin and clavulanic acid) was effective in treating acute uncomplicated appendicitis in 166 children, with 98% showing clinical improvement and only 4 requiring surgery during initial hospitalization.

The study demonstrated that non-operative treatment is a safe alternative for managing uncomplicated appendicitis, with a low rate of complications and a 13.25% recurrence rate of appendicitis during a median follow-up of 18.8 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-operative Management for Uncomplicated Appendicitis: An Option to Consider. Abbo, O., Trabanino, C., Pinnagoda, K., et al.[2018]

A study involving 1066 patients with complex appendicitis found that 2 days of postoperative intravenous antibiotics is as effective as 5 days in preventing infectious complications and mortality, with a non-inferiority margin of 7.5%.

Patients receiving the shorter 2-day antibiotic treatment experienced significantly fewer adverse effects (9% vs. 22%) compared to those on the 5-day regimen, suggesting a safer and more efficient approach to postoperative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial. de Wijkerslooth, EML., Boerma, EG., van Rossem, CC., et al.[2023]

This study aims to determine if a short course of 48 hours of postoperative antibiotics is as effective as the standard 5-day course in preventing infectious complications after appendectomy in patients with complex appendicitis, involving 1066 participants aged 8 years and older.

If the 48-hour antibiotic treatment is found to be non-inferior, it could lead to changes in clinical guidelines, reducing unnecessary antibiotic use and addressing concerns about antimicrobial resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two versus five days of antibiotics after appendectomy for complex acute appendicitis (APPIC): study protocol for a randomized controlled trial. van den Boom, AL., de Wijkerslooth, EML., van Rosmalen, J., et al.[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]

A retrospective review of appendicitis cases showed that a shorter duration of antibiotics (4.1 days) after surgery for complicated appendicitis significantly reduced the 30-day readmission rate to 2%, compared to 16% with longer antibiotic treatment (5.5 days).

The study found no significant difference in hospital stay duration (approximately 6.1 days) or in-hospital infectious complications between the shorter and longer antibiotic treatment groups, suggesting that shorter antibiotic courses are safe and effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perforated appendicitis: Short duration antibiotics are noninferior to traditional long duration antibiotics. David, A., Dodgion, C., Zein Eddine, SB., et al.[2020]

References

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

Antibiotic Duration After Laparoscopic Appendectomy for Acute Complicated Appendicitis. [2016]

2. France pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Duration of antibiotic treatment after appendicectomy for acute complicated appendicitis. [2022]

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

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

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

The efficacy of postoperative oral antibiotics in appendicitis: a randomized prospective double-blinded study. [2013]

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

Patient Factors Associated With Appendectomy Within 30 Days of Initiating Antibiotic Treatment for Appendicitis. [2023]

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

Long-Term Results Following Antibiotic Treatment of Acute Appendicitis in Adults. [2022]

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

Outcomes of Antibiotic Therapy for Uncomplicated Appendicitis in Pregnancy. [2018]

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

Non-operative Management for Uncomplicated Appendicitis: An Option to Consider. [2018]

10. England pubmed.ncbi.nlm.nih.gov

2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Two versus five days of antibiotics after appendectomy for complex acute appendicitis (APPIC): study protocol for a randomized controlled trial. [2019]

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

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

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

Perforated appendicitis: Short duration antibiotics are noninferior to traditional long duration antibiotics. [2020]