Trial Outcomes & Findings for The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) Trial (NCT NCT02800785)

Last Updated: 2023-05-06

Results Overview

The primary evaluation of patient-reported quality of life, as measured by the EuroQuol-5D at four-weeks, will be conducted using an intention-to-treat (ITT) analysis, where patients' data are analyzed according to the patients' randomized treatment assignment. EQ5D assesses health status in terms of five dimensions of health. The maximum score of 1 indicates the best health state, the minimum score is 0 (as score as bad as being dead).

Recruitment status

COMPLETED

Study phase

Target enrollment

1552 participants

Primary outcome timeframe

Four-weeks after randomization

Results posted on

2023-05-06

Participant Flow

Participant milestones

Participant milestones
Measure	Antibiotics Therapy Arm Patients in the antibiotics (abx) arm will receive a total of 10 days of abx, with a minimum of 24 hours using an IV abx formulation (administered in q8, q12, or q24 hour regimens with or without concurrent oral abx) followed by oral abx for the remainder of the 10 days. Pts will be offered a treatment regimen of abx based on guidelines published jointly by the Surgical Infection Society and the Infectious Disease Society of America. Any of the IV abx options (Single antibiotic-Cefoxitin, Ertapenem, Moxifloxicin, Tigecycline, Ticarcillin-Clavulanic Acid or Dual antibiotics-Metronidazole plus one of the following-Cefazolin, Cefuroxime, Ceftriaxone, Cefotaxime, Ciprofloxacin, Levofloxacin) will be considered acceptable. After IV abx, a regimen of oral abx will be continued for a total treatment length of 10 days.	Appendectomy Arm Patients in the appendectomy arm will have an appendectomy performed by an open or laparoscopic approach, depending on patient and surgeon preference. Prior to their operation, patients in this arm will receive one dose of antibiotics per currently accepted standards when appendicitis diagnosis is confirmed. Patients may also receive preoperative antibiotics per hospital standards for surgical infection prevention bundle. Appendectomy: Appendectomy will be performed by an open or laparoscopic approach, depending on patient and surgeon preference.
Overall Study STARTED	776	776
Overall Study 30 Day Follow up	702	695
Overall Study COMPLETED	676	656
Overall Study NOT COMPLETED	100	120

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Antibiotics Therapy Arm n=776 Participants Patients in the antibiotics (abx) arm will receive a total of 10 days of abx, with a minimum of 24 hours using an IV abx formulation (administered in q8, q12, or q24 hour regimens with or without concurrent oral abx) followed by oral abx for the remainder of the 10 days. Patients will be offered a treatment regimen of abx based on guidelines published jointly by the Surgical Infection Society and the Infectious Disease Society of America. Any of the IV abx options (Single antibiotic-Cefoxitin, Ertapenem, Moxifloxicin, Tigecycline, Ticarcillin-Clavulanic Acid or Dual antibiotics-Metronidazole plus one of the following-Cefazolin, Cefuroxime, Ceftriaxone, Cefotaxime, Ciprofloxacin, Levofloxacin) will be considered acceptable. After IV abx, a regimen of oral abx will be continued for a total treatment length of 10 days.	Appendectomy Arm n=776 Participants Patients in the appendectomy arm will have an appendectomy performed by an open or laparoscopic approach, depending on patient and surgeon preference. Prior to their operation, patients in this arm will receive one dose of antibiotics per currently accepted standards when appendicitis diagnosis is confirmed. Patients may also receive preoperative antibiotics per hospital standards for surgical infection prevention bundle. Appendectomy: Appendectomy will be performed by an open or laparoscopic approach, depending on patient and surgeon preference.	Total n=1552 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	745 Participants n=5 Participants	748 Participants n=7 Participants	1493 Participants n=5 Participants
Age, Categorical >=65 years	31 Participants n=5 Participants	28 Participants n=7 Participants	59 Participants n=5 Participants
Age, Continuous	38.3 Years STANDARD_DEVIATION 13.4 • n=5 Participants	37.8 Years STANDARD_DEVIATION 13.7 • n=7 Participants	38.1 Years STANDARD_DEVIATION 13.5 • n=5 Participants
Sex/Gender, Customized Gender different from sex assigned at birth	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Female	286 Participants n=5 Participants	290 Participants n=7 Participants	576 Participants n=5 Participants
Sex: Female, Male Male	490 Participants n=5 Participants	486 Participants n=7 Participants	976 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	13 Participants n=5 Participants	9 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) Asian	39 Participants n=5 Participants	53 Participants n=7 Participants	92 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Black or African American	75 Participants n=5 Participants	63 Participants n=7 Participants	138 Participants n=5 Participants
Race (NIH/OMB) White	461 Participants n=5 Participants	449 Participants n=7 Participants	910 Participants n=5 Participants
Race (NIH/OMB) More than one race	176 Participants n=5 Participants	185 Participants n=7 Participants	361 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	14 Participants n=7 Participants	22 Participants n=5 Participants
Region of Enrollment United States	776 participants n=5 Participants	776 participants n=7 Participants	1552 participants n=5 Participants

PRIMARY outcome

Timeframe: Four-weeks after randomization

Population: The overall number of participants in each arm represents the number of participants who responded to the EQ-5D questions on the 4 week survey

Outcome measures

Outcome measures
Measure	Antibiotics Therapy Arm n=683 Participants Patients in the antibiotics (abx) arm will receive a total of 10 days of abx, with a minimum of 24 hours using an IV abx formulation (administered in q8, q12, or q24 hour regimens with or without concurrent oral abx) followed by oral abx for the remainder of the 10 days. Patients will be offered a treatment regimen of abx based on guidelines published jointly by the Surgical Infection Society and the Infectious Disease Society of America. Any of the IV abx options (Single antibiotic-Cefoxitin, Ertapenem, Moxifloxicin, Tigecycline, Ticarcillin-Clavulanic Acid or Dual antibiotics-Metronidazole plus one of the following-Cefazolin, Cefuroxime, Ceftriaxone, Cefotaxime, Ciprofloxacin, Levofloxacin) will be considered acceptable. After IV abx, a regimen of oral abx will be continued for a total treatment length of 10 days.	Appendectomy Arm n=664 Participants Patients in the appendectomy arm will have an appendectomy performed by an open or laparoscopic approach, depending on patient and surgeon preference. Prior to their operation, patients in this arm will receive one dose of antibiotics per currently accepted standards when appendicitis diagnosis is confirmed. Patients may also receive preoperative antibiotics per hospital standards for surgical infection prevention bundle.
Patient-reported Quality of Life as Measured by EuroQol (EQ-5D)	0.92 score on a scale Standard Deviation 0.13	0.91 score on a scale Standard Deviation 0.13

SECONDARY outcome

Timeframe: at 30 days

Population: Patients in each arm are reflective of the total n (participants) who responded to the appendicitis symptoms questions in the 4 week survey.

Total Number of Patients who had resolution of appendicitis symptoms at 30 Days. This was measured as absence of fever and abdominal pain and tenderness.

Outcome measures

Outcome measures
Measure	Antibiotics Therapy Arm n=676 Participants Patients in the antibiotics (abx) arm will receive a total of 10 days of abx, with a minimum of 24 hours using an IV abx formulation (administered in q8, q12, or q24 hour regimens with or without concurrent oral abx) followed by oral abx for the remainder of the 10 days. Patients will be offered a treatment regimen of abx based on guidelines published jointly by the Surgical Infection Society and the Infectious Disease Society of America. Any of the IV abx options (Single antibiotic-Cefoxitin, Ertapenem, Moxifloxicin, Tigecycline, Ticarcillin-Clavulanic Acid or Dual antibiotics-Metronidazole plus one of the following-Cefazolin, Cefuroxime, Ceftriaxone, Cefotaxime, Ciprofloxacin, Levofloxacin) will be considered acceptable. After IV abx, a regimen of oral abx will be continued for a total treatment length of 10 days.	Appendectomy Arm n=663 Participants Patients in the appendectomy arm will have an appendectomy performed by an open or laparoscopic approach, depending on patient and surgeon preference. Prior to their operation, patients in this arm will receive one dose of antibiotics per currently accepted standards when appendicitis diagnosis is confirmed. Patients may also receive preoperative antibiotics per hospital standards for surgical infection prevention bundle.
Total Number of Patients Who Had Resolution of Appendicitis Symptoms at 30 Days	462 Participants	466 Participants

SECONDARY outcome

Timeframe: 90 days post enrollment

Population: Overall Number of Participants in each arm is reflective those participants who had surgery by 90 days post enrollment.

Rates of patients who had perforated appendicitis will be calculated for each arm among those received an appendectomy.

Outcome measures

Outcome measures
Measure	Antibiotics Therapy Arm n=185 Participants Patients in the antibiotics (abx) arm will receive a total of 10 days of abx, with a minimum of 24 hours using an IV abx formulation (administered in q8, q12, or q24 hour regimens with or without concurrent oral abx) followed by oral abx for the remainder of the 10 days. Patients will be offered a treatment regimen of abx based on guidelines published jointly by the Surgical Infection Society and the Infectious Disease Society of America. Any of the IV abx options (Single antibiotic-Cefoxitin, Ertapenem, Moxifloxicin, Tigecycline, Ticarcillin-Clavulanic Acid or Dual antibiotics-Metronidazole plus one of the following-Cefazolin, Cefuroxime, Ceftriaxone, Cefotaxime, Ciprofloxacin, Levofloxacin) will be considered acceptable. After IV abx, a regimen of oral abx will be continued for a total treatment length of 10 days.	Appendectomy Arm n=621 Participants Patients in the appendectomy arm will have an appendectomy performed by an open or laparoscopic approach, depending on patient and surgeon preference. Prior to their operation, patients in this arm will receive one dose of antibiotics per currently accepted standards when appendicitis diagnosis is confirmed. Patients may also receive preoperative antibiotics per hospital standards for surgical infection prevention bundle.
Rate of Participants With Perforated Appendicitis	59 Participants	99 Participants

SECONDARY outcome

Timeframe: 90 days

Population: Total n of participants in each arm is reflective of those participants who completed the 90 day survey.

Comparison of the number of participants with at least one surgical complication and antibiotic complications.

Outcome measures

Outcome measures
Measure	Antibiotics Therapy Arm n=676 Participants Patients in the antibiotics (abx) arm will receive a total of 10 days of abx, with a minimum of 24 hours using an IV abx formulation (administered in q8, q12, or q24 hour regimens with or without concurrent oral abx) followed by oral abx for the remainder of the 10 days. Patients will be offered a treatment regimen of abx based on guidelines published jointly by the Surgical Infection Society and the Infectious Disease Society of America. Any of the IV abx options (Single antibiotic-Cefoxitin, Ertapenem, Moxifloxicin, Tigecycline, Ticarcillin-Clavulanic Acid or Dual antibiotics-Metronidazole plus one of the following-Cefazolin, Cefuroxime, Ceftriaxone, Cefotaxime, Ciprofloxacin, Levofloxacin) will be considered acceptable. After IV abx, a regimen of oral abx will be continued for a total treatment length of 10 days.	Appendectomy Arm n=656 Participants Patients in the appendectomy arm will have an appendectomy performed by an open or laparoscopic approach, depending on patient and surgeon preference. Prior to their operation, patients in this arm will receive one dose of antibiotics per currently accepted standards when appendicitis diagnosis is confirmed. Patients may also receive preoperative antibiotics per hospital standards for surgical infection prevention bundle.
Number of Participants With at Least One Complications From Treatment	37 Participants	21 Participants

SECONDARY outcome

Timeframe: Through study completion, up to 2 years

Population: Total number of participants is reflective of participants randomized to each arm.

Rates of appendiceal cancer among participants will be calculated among the antibiotics and appendectomy arms.

Outcome measures

Outcome measures
Measure	Antibiotics Therapy Arm n=776 Participants Patients in the antibiotics (abx) arm will receive a total of 10 days of abx, with a minimum of 24 hours using an IV abx formulation (administered in q8, q12, or q24 hour regimens with or without concurrent oral abx) followed by oral abx for the remainder of the 10 days. Patients will be offered a treatment regimen of abx based on guidelines published jointly by the Surgical Infection Society and the Infectious Disease Society of America. Any of the IV abx options (Single antibiotic-Cefoxitin, Ertapenem, Moxifloxicin, Tigecycline, Ticarcillin-Clavulanic Acid or Dual antibiotics-Metronidazole plus one of the following-Cefazolin, Cefuroxime, Ceftriaxone, Cefotaxime, Ciprofloxacin, Levofloxacin) will be considered acceptable. After IV abx, a regimen of oral abx will be continued for a total treatment length of 10 days.	Appendectomy Arm n=776 Participants Patients in the appendectomy arm will have an appendectomy performed by an open or laparoscopic approach, depending on patient and surgeon preference. Prior to their operation, patients in this arm will receive one dose of antibiotics per currently accepted standards when appendicitis diagnosis is confirmed. Patients may also receive preoperative antibiotics per hospital standards for surgical infection prevention bundle.
Rates of Participants With Appendiceal Cancer	4 Participants	6 Participants

SECONDARY outcome

Timeframe: 90 days post randomization

Population: Number of Participants in each arm is reflective of participants who completed the 90 day survey question regarding days in the hospital.

Mean number of days in the hospital per participant calculated at 90 days post randomization. (Number of days/Number of Participants in Therapy Arm who responded to the 90 day survey question)

Outcome measures

Outcome measures
Measure	Antibiotics Therapy Arm n=622 Participants Patients in the antibiotics (abx) arm will receive a total of 10 days of abx, with a minimum of 24 hours using an IV abx formulation (administered in q8, q12, or q24 hour regimens with or without concurrent oral abx) followed by oral abx for the remainder of the 10 days. Patients will be offered a treatment regimen of abx based on guidelines published jointly by the Surgical Infection Society and the Infectious Disease Society of America. Any of the IV abx options (Single antibiotic-Cefoxitin, Ertapenem, Moxifloxicin, Tigecycline, Ticarcillin-Clavulanic Acid or Dual antibiotics-Metronidazole plus one of the following-Cefazolin, Cefuroxime, Ceftriaxone, Cefotaxime, Ciprofloxacin, Levofloxacin) will be considered acceptable. After IV abx, a regimen of oral abx will be continued for a total treatment length of 10 days.	Appendectomy Arm n=609 Participants Patients in the appendectomy arm will have an appendectomy performed by an open or laparoscopic approach, depending on patient and surgeon preference. Prior to their operation, patients in this arm will receive one dose of antibiotics per currently accepted standards when appendicitis diagnosis is confirmed. Patients may also receive preoperative antibiotics per hospital standards for surgical infection prevention bundle.
Days in Hospital After Index Treatment Within 90 Days	0.68 Days per participant (rate) Interval -3.36 to 4.72	0.15 Days per participant (rate) Interval -2.05 to 2.35

SECONDARY outcome

Timeframe: 90 days post randomization

Population: Number of Participants in each arm is reflective of participants who completed the 90 day survey question regarding clinic or emergency room visits.

Total number of participants with any visit to emergency department or urgent care clinic after index treatment within 90 days

Outcome measures

Outcome measures
Measure	Antibiotics Therapy Arm n=618 Participants Patients in the antibiotics (abx) arm will receive a total of 10 days of abx, with a minimum of 24 hours using an IV abx formulation (administered in q8, q12, or q24 hour regimens with or without concurrent oral abx) followed by oral abx for the remainder of the 10 days. Patients will be offered a treatment regimen of abx based on guidelines published jointly by the Surgical Infection Society and the Infectious Disease Society of America. Any of the IV abx options (Single antibiotic-Cefoxitin, Ertapenem, Moxifloxicin, Tigecycline, Ticarcillin-Clavulanic Acid or Dual antibiotics-Metronidazole plus one of the following-Cefazolin, Cefuroxime, Ceftriaxone, Cefotaxime, Ciprofloxacin, Levofloxacin) will be considered acceptable. After IV abx, a regimen of oral abx will be continued for a total treatment length of 10 days.	Appendectomy Arm n=604 Participants Patients in the appendectomy arm will have an appendectomy performed by an open or laparoscopic approach, depending on patient and surgeon preference. Prior to their operation, patients in this arm will receive one dose of antibiotics per currently accepted standards when appendicitis diagnosis is confirmed. Patients may also receive preoperative antibiotics per hospital standards for surgical infection prevention bundle.
Number of Clinic Visits or Emergency Room Visits	55 visits	26 visits

SECONDARY outcome

Timeframe: 90 days post randomization

Population: Total Number of participants randomized to antibiotics

incidence proportion of appendectomy within 90 days post randomization among those randomized to antibiotics

Outcome measures

Outcome measures
Measure	Antibiotics Therapy Arm n=776 Participants Patients in the antibiotics (abx) arm will receive a total of 10 days of abx, with a minimum of 24 hours using an IV abx formulation (administered in q8, q12, or q24 hour regimens with or without concurrent oral abx) followed by oral abx for the remainder of the 10 days. Patients will be offered a treatment regimen of abx based on guidelines published jointly by the Surgical Infection Society and the Infectious Disease Society of America. Any of the IV abx options (Single antibiotic-Cefoxitin, Ertapenem, Moxifloxicin, Tigecycline, Ticarcillin-Clavulanic Acid or Dual antibiotics-Metronidazole plus one of the following-Cefazolin, Cefuroxime, Ceftriaxone, Cefotaxime, Ciprofloxacin, Levofloxacin) will be considered acceptable. After IV abx, a regimen of oral abx will be continued for a total treatment length of 10 days.	Appendectomy Arm Patients in the appendectomy arm will have an appendectomy performed by an open or laparoscopic approach, depending on patient and surgeon preference. Prior to their operation, patients in this arm will receive one dose of antibiotics per currently accepted standards when appendicitis diagnosis is confirmed. Patients may also receive preoperative antibiotics per hospital standards for surgical infection prevention bundle.
Eventual Appendectomy Incidence Proportion	0.29 incidence proportion Interval 0.26 to 0.32	—

Adverse Events

Antibiotics Therapy Arm

Serious events: 19 serious events

Other events: 26 other events

Deaths: 0 deaths

Appendectomy Arm

Serious events: 19 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Antibiotics Therapy Arm n=676 participants at risk Patients in the antibiotics (abx) arm will receive a total of 10 days of abx, with a minimum of 24 hours using an IV abx formulation (administered in q8, q12, or q24 hour regimens with or without concurrent oral abx) followed by oral abx for the remainder of the 10 days. Patients will be offered a treatment regimen of abx based on guidelines published jointly by the Surgical Infection Society and the Infectious Disease Society of America. Any of the IV abx options (Single antibiotic-Cefoxitin, Ertapenem, Moxifloxicin, Tigecycline, Ticarcillin-Clavulanic Acid or Dual antibiotics-Metronidazole plus one of the following-Cefazolin, Cefuroxime, Ceftriaxone, Cefotaxime, Ciprofloxacin, Levofloxacin) will be considered acceptable. After IV abx, a regimen of oral abx will be continued for a total treatment length of 10 days.	Appendectomy Arm n=656 participants at risk Patients in the appendectomy arm will have an appendectomy performed by an open or laparoscopic approach, depending on patient and surgeon preference. Prior to their operation, patients in this arm will receive one dose of antibiotics per currently accepted standards when appendicitis diagnosis is confirmed. Patients may also receive preoperative antibiotics per hospital standards for surgical infection prevention bundle. Appendectomy: Appendectomy will be performed by an open or laparoscopic approach, depending on patient and surgeon preference.
General disorders Unplanned hospitalization not for appendectomy	2.8% 19/676 • Number of events 27 • Adverse events from enrollment to 90 days. Total number of participants at risk is reflective of number of participant who completed a survey at 90 days post randomization.	2.9% 19/656 • Number of events 20 • Adverse events from enrollment to 90 days. Total number of participants at risk is reflective of number of participant who completed a survey at 90 days post randomization.

Other adverse events

Other adverse events
Measure	Antibiotics Therapy Arm n=676 participants at risk Patients in the antibiotics (abx) arm will receive a total of 10 days of abx, with a minimum of 24 hours using an IV abx formulation (administered in q8, q12, or q24 hour regimens with or without concurrent oral abx) followed by oral abx for the remainder of the 10 days. Patients will be offered a treatment regimen of abx based on guidelines published jointly by the Surgical Infection Society and the Infectious Disease Society of America. Any of the IV abx options (Single antibiotic-Cefoxitin, Ertapenem, Moxifloxicin, Tigecycline, Ticarcillin-Clavulanic Acid or Dual antibiotics-Metronidazole plus one of the following-Cefazolin, Cefuroxime, Ceftriaxone, Cefotaxime, Ciprofloxacin, Levofloxacin) will be considered acceptable. After IV abx, a regimen of oral abx will be continued for a total treatment length of 10 days.	Appendectomy Arm n=656 participants at risk Patients in the appendectomy arm will have an appendectomy performed by an open or laparoscopic approach, depending on patient and surgeon preference. Prior to their operation, patients in this arm will receive one dose of antibiotics per currently accepted standards when appendicitis diagnosis is confirmed. Patients may also receive preoperative antibiotics per hospital standards for surgical infection prevention bundle. Appendectomy: Appendectomy will be performed by an open or laparoscopic approach, depending on patient and surgeon preference.
General disorders Reaction to antibiotics that led to a health care encounter	3.3% 22/676 • Number of events 676 • Adverse events from enrollment to 90 days. Total number of participants at risk is reflective of number of participant who completed a survey at 90 days post randomization.	0.15% 1/656 • Number of events 656 • Adverse events from enrollment to 90 days. Total number of participants at risk is reflective of number of participant who completed a survey at 90 days post randomization.
General disorders Clostridioides difficile colitis	0.59% 4/676 • Number of events 4 • Adverse events from enrollment to 90 days. Total number of participants at risk is reflective of number of participant who completed a survey at 90 days post randomization.	0.61% 4/656 • Number of events 4 • Adverse events from enrollment to 90 days. Total number of participants at risk is reflective of number of participant who completed a survey at 90 days post randomization.

Additional Information

Erin Fannon

University of Washington

Phone: 206-685-9770

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place