Ignite Creation Date:
2024-05-05 @ 11:57 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00195923
Status:
COMPLETED
Last Update Posted:
2007-04-06
First Post:
2005-09-12
Brief Title:
Prospective Randomized Evaluation of Antibiotic Regimen Following Appendectomy for Perforated Appendicitis
Sponsor:
Childrens Mercy Hospital Kansas City
Organization:
Childrens Mercy Hospital Kansas City
Study Overview
Official Title:
Prospective Randomized Evaluation of Antibiotic Regimen Following Appendectomy for Perforated Appendicitis
Status:
COMPLETED
Status Verified Date:
2005-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to compare traditional triple antibiotic therapy against dual single day dosing antibiotic therapy in the management of perforated appendicitis in children
Detailed Description:
Triple antibiotic therapy providing broad spectrum coverage of gram positive gram negative and anaerobic bacteria has long been the standard treatment for perforated appendicitis in children This regimen has traditionally consisted of ampicillin gentamicin and clindamycin The dosing regimen for these medications are quite frequent as follows ampicillin every 6 hours gentamicin every 8 hours and clindamycin every 8 hours until there is no evidence for postoperative infection usually 5 to 7 days Further gentamicin is an aminoglycoside with known renal and ototoxic side effects Its therapeutic window is small necessitating measurement of serum levels to maintain therapeutic levels and avoid toxicity The contemporary selection of antibiotics includes very few drugs that require such monitoring
Monotherapy with newer broad-spectrum agents such as piperacillintazobactam for intraabdominal infections has recently been demonstrated to be equally efficacious as traditional triple therapy Such data calls into question the need for such onerous antibiotic regimens which include a nephrotoxic agent gentamycin However the benefits of monotherapy are outweighed by the increased expense of the antibiotic and the ongoing cumbersome dosing schedule of 3-4 doses daily We have recently moved to a dual antibiotic regimen ceftriaxone and metronidazole which provides excellent antimicrobial coverage and can be dosed on a once daily dosing schedule with an identical duration of therapy as for the triple antibiotic regimen This regimen has proven effective in adults with intraabdominal infections such as perforated appendicitis Further ceftriaxone plus metronidazole has been shown equal to the aforementioned monotherapy schedule with piperacillintazobactam in children with complicated perforated appendicitis The advantages of dual antibiotic therapy with once a day dosing for children with perforated appendicitis are immense especially if the antibiotics are well tolerated less expensive and have a simple dosing schedule Additionally neither drug is nephrotoxic both have broad therapeutic ranges and therefore require no serum level measurements This translates into less blood draws less time patients need to be receiving infusions and less utilization of nursing resources These advantages would be expected to culminate in greater nursing and patient satisfaction The purpose of this study is to scientifically compare the traditional triple antibiotic regimen to dual antibiotic regimen for children with perforated appendicitis quantify its significance and report our findings to physicians caring for these children
This will be a prospective randomized study involving children who undergo appendectomy for perforated appendicitis All patients will receive antibiotics ceftriaxone and flagyl preoperatively The determination of perforation will be made by the surgeon at the time of the operation Perforation will be determined by either identifying a perforation in the appendix itself or by identifying anaerobic odors emanating from the abdominal cavity during operation sniff test Once perforated appendicitis has been documented the parentsguardians of the patient will be informed of the option to participate in the prospective randomized study Patients whose parents agree and consent to enroll in the study will then be randomized to one of 2 groups based on a sequential randomization number created by Steve Simon PhD
Based on a power analysis of length of stay performed by Dr Simon 50 patients in each of the two arms of the study will provide a power of 82 with an alpha level of 005 Dr Simon feels that this level is appropriate for this study
The control group will consist of triple antibiotic coverage with ampicillin 50mgkg every 6 hours gentamicin 25 mgkg every 8 hours and clindamycin 10mgkg every 6 hours which are standard dosing regimens The experimental group will receive ceftriaxone 50mgkg once a day maximum dose 2 grams and metronidazole 30mgkg once a day maximum dose 1 gram with once a day dosing for both The length of antibiotic therapy will not differ from our standard management and will remain standardized in both arms All patients will receive a minimum of 5 days of therapy regardless of group randomization At that time if they have been afebrile for at least 24 hours a white blood cell WBC count will be obtained and if that is within normal limits the antibiotics will be discontinued If after 5 days of therapy the patient remains febrile therapy will continue without change unless cultures obtained from the febrile response indicate a need for antibiotic coverage change If a change in antibiotic regimen is indicated the antibiotic profile will be evaluated and the most appropriate antibiotic will be instituted If this occurs the patients data will continue to be collected in an intention to treat analysis In cases where there is no indication for a change in antibiotic regimen a WBC count will be drawn once the patient has become and remains afebrile for a complete 24 hour period of time If the WBC is elevated the antibiotic course will continue with WBC counts to be drawn daily until normal values return If leukocytosis or fever persists for 10 days or if there is clinical indication of a postoperative intra-abdominal infection a CT scan of the abdomen and pelvis will be performed to determine if a postoperative abscess has developed Identification of a postoperative abscess will result in percutaneous drainage with culture and sensitivity of the abscess fluid Subsequent antibiotic treatment will be based on the sensitivities obtained from the culture of the abscess In these cases the patients data will be collected and they will be regarded as a failure of antibiotic therapy in the final analysis
Parental permission and child assent if the child is old enough will be obtained see attached form and patients will be randomized to the control or experimental group based on a randomization number generated by Dr Steve Simon PhD Patient demographics operative approach time to tolerating full feeds length of hospitalization infectious complications medication charges and hospital charges will be collected for comparison between the groups
Monotherapy with newer broad-spectrum agents such as piperacillintazobactam for intraabdominal infections has recently been demonstrated to be equally efficacious as traditional triple therapy Such data calls into question the need for such onerous antibiotic regimens which include a nephrotoxic agent gentamycin However the benefits of monotherapy are outweighed by the increased expense of the antibiotic and the ongoing cumbersome dosing schedule of 3-4 doses daily We have recently moved to a dual antibiotic regimen ceftriaxone and metronidazole which provides excellent antimicrobial coverage and can be dosed on a once daily dosing schedule with an identical duration of therapy as for the triple antibiotic regimen This regimen has proven effective in adults with intraabdominal infections such as perforated appendicitis Further ceftriaxone plus metronidazole has been shown equal to the aforementioned monotherapy schedule with piperacillintazobactam in children with complicated perforated appendicitis The advantages of dual antibiotic therapy with once a day dosing for children with perforated appendicitis are immense especially if the antibiotics are well tolerated less expensive and have a simple dosing schedule Additionally neither drug is nephrotoxic both have broad therapeutic ranges and therefore require no serum level measurements This translates into less blood draws less time patients need to be receiving infusions and less utilization of nursing resources These advantages would be expected to culminate in greater nursing and patient satisfaction The purpose of this study is to scientifically compare the traditional triple antibiotic regimen to dual antibiotic regimen for children with perforated appendicitis quantify its significance and report our findings to physicians caring for these children
This will be a prospective randomized study involving children who undergo appendectomy for perforated appendicitis All patients will receive antibiotics ceftriaxone and flagyl preoperatively The determination of perforation will be made by the surgeon at the time of the operation Perforation will be determined by either identifying a perforation in the appendix itself or by identifying anaerobic odors emanating from the abdominal cavity during operation sniff test Once perforated appendicitis has been documented the parentsguardians of the patient will be informed of the option to participate in the prospective randomized study Patients whose parents agree and consent to enroll in the study will then be randomized to one of 2 groups based on a sequential randomization number created by Steve Simon PhD
Based on a power analysis of length of stay performed by Dr Simon 50 patients in each of the two arms of the study will provide a power of 82 with an alpha level of 005 Dr Simon feels that this level is appropriate for this study
The control group will consist of triple antibiotic coverage with ampicillin 50mgkg every 6 hours gentamicin 25 mgkg every 8 hours and clindamycin 10mgkg every 6 hours which are standard dosing regimens The experimental group will receive ceftriaxone 50mgkg once a day maximum dose 2 grams and metronidazole 30mgkg once a day maximum dose 1 gram with once a day dosing for both The length of antibiotic therapy will not differ from our standard management and will remain standardized in both arms All patients will receive a minimum of 5 days of therapy regardless of group randomization At that time if they have been afebrile for at least 24 hours a white blood cell WBC count will be obtained and if that is within normal limits the antibiotics will be discontinued If after 5 days of therapy the patient remains febrile therapy will continue without change unless cultures obtained from the febrile response indicate a need for antibiotic coverage change If a change in antibiotic regimen is indicated the antibiotic profile will be evaluated and the most appropriate antibiotic will be instituted If this occurs the patients data will continue to be collected in an intention to treat analysis In cases where there is no indication for a change in antibiotic regimen a WBC count will be drawn once the patient has become and remains afebrile for a complete 24 hour period of time If the WBC is elevated the antibiotic course will continue with WBC counts to be drawn daily until normal values return If leukocytosis or fever persists for 10 days or if there is clinical indication of a postoperative intra-abdominal infection a CT scan of the abdomen and pelvis will be performed to determine if a postoperative abscess has developed Identification of a postoperative abscess will result in percutaneous drainage with culture and sensitivity of the abscess fluid Subsequent antibiotic treatment will be based on the sensitivities obtained from the culture of the abscess In these cases the patients data will be collected and they will be regarded as a failure of antibiotic therapy in the final analysis
Parental permission and child assent if the child is old enough will be obtained see attached form and patients will be randomized to the control or experimental group based on a randomization number generated by Dr Steve Simon PhD Patient demographics operative approach time to tolerating full feeds length of hospitalization infectious complications medication charges and hospital charges will be collected for comparison between the groups
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None