APPAC

Population

• Adults 18 to 60 years old with uncomplicated acute appendicitis confirmed by CT.

Intervention

Intravenous ertapenem 1 g daily for 3 days, followed by 7 days of oral levofloxacin 500 mg once daily and metronidazole 500 mg three times daily.

Comparator

Standard open appendectomy.

Key results

• Among 530 enrolled patients, 273 were assigned to surgery and 257 to antibiotics. Successful appendectomy occurred in all but 1 surgical patient (99.6%; 95% CI 98.0%-100.0%).
• In the antibiotic group, 70 patients (27.3%; 95% CI 22.0%-33.2%) underwent appendectomy within 1 year. Of 256 antibiotic-group patients available for follow-up, 186 (72.7%; 95% CI 66.8%-78.0%) did not require surgery.
• The intention-to-treat difference in treatment efficacy was -27.0% (95% CI -31.6% to infinity; P=0.89). Against a prespecified 24% noninferiority margin, noninferiority of antibiotics relative to surgery was not demonstrated.
• Of the 70 antibiotic-assigned patients who later had appendectomy, 58 (82.9%) had uncomplicated appendicitis, 7 (10.0%) had complicated acute appendicitis, and 5 (7.1%) did not have appendicitis.

Harms

• There were no intra-abdominal abscesses or other major complications associated with delayed appendectomy in patients randomized to antibiotic treatment.

Practice impact

• Do not tell patients that APPAC proved antibiotics are as good as appendectomy. Noninferiority was not demonstrated.
• It is fair to say that most patients assigned to antibiotics did not need appendectomy during 1 year, and delayed operations in this trial were not associated with intra-abdominal abscess or other major complications.

Applicability

• Most applicable to adults 18 to 60 years old in Finland with CT-proven uncomplicated appendicitis, treated with this ertapenem-then-levofloxacin-metronidazole regimen or with open appendectomy.

Limitations

• The trial was open-label.
• The surgical comparator was standard open appendectomy, not laparoscopic surgery.
• One-year follow-up was available for 256 of 257 patients in the antibiotic group.
• The primary end point was defined differently in each arm, and the noninferiority comparison did not meet the 24% margin.

Common misinterpretations

• Avoiding surgery in most antibiotic-assigned patients is not the same as meeting noninferiority versus appendectomy.
• APPAC does not establish antibiotics as equivalent to surgery for uncomplicated appendicitis.