Ignite Creation Date:
2024-05-06 @ 10:25 AM
Last Modification Date:
2024-10-26 @ 12:30 PM
Study NCT ID:
NCT03257423
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2020-11-10
First Post:
2017-08-02
Brief Title:
Acute Appendicitis and Microbiota - Etiology of Appendicitis and Antibiotic Therapy Effects
Sponsor:
Turku University Hospital
Organization:
Turku University Hospital
Study Overview
Official Title:
Acute Appendicitis and Microbiota - Ethology of Appendicitis and Effects of the Antimicrobial Treatment - The MAPPAC Microbiology Appendicitis Acuta Trial
Status:
ENROLLING_BY_INVITATION
Status Verified Date:
2020-11
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:
MAPPAC
Brief Summary:
Appendicectomy has been the treatment of acute appendicitis for over a hundred years Appendicectomy however includes operative and postoperative risks despite being a routine procedure Several studies have proved promising results of the safety and efficiency of antibiotics in the treatment of acute uncomplicated appendicitis The previous APPAC study by the investigators published in 2015 in the Journal of American Medical Association also proved promising results with 73 of patients with uncomplicated appendicitis treated successfully with antibiotics None of the patients initially treated with antibiotics that later had appendectomy had major complications The results of the APPAC trial suggest that CT proven uncomplicated acute appendicitis is not a surgical emergency and antibiotic therapy is a safe first-line treatment option Reducing unnecessary appendectomies has also been shown to lead to significant economic savings On the other hand antibiotic therapies have been shown to have an effect on the normal gut microbiota and are considered an increasing global health threat underlining the importance of evaluating both short- and long-term effects of the antimicrobial treatment in old and new indications
The aims of this randomized prospective study are
1 To evaluate the possible role and differences in the microbiological etiology of complicated and uncomplicated appendicitis
2 To determine the effects of both antibiotic and placebo treatment on the composition of gut microbiota and to evaluate how it recovers after the appendicitis-related antimicrobial treatment AMT
3 To evaluate the effects of the duration of the hospital stay on the AMR reservoir of the gut microbiota
The aims of this randomized prospective study are
1 To evaluate the possible role and differences in the microbiological etiology of complicated and uncomplicated appendicitis
2 To determine the effects of both antibiotic and placebo treatment on the composition of gut microbiota and to evaluate how it recovers after the appendicitis-related antimicrobial treatment AMT
3 To evaluate the effects of the duration of the hospital stay on the AMR reservoir of the gut microbiota
Detailed Description:
Appendectomy has been the treatment of acute appendicitis for over a hundred years Appendicectomy however includes operative and postoperative risks despite being a routine procedure Several studies have proved promising results of the safety and efficiency of antibiotics in the treatment of acute uncomplicated appendicitis The previous APPAC study by the investigators published in 2015 in the Journal of American Medical Association also proved promising results with 73 of patients with uncomplicated appendicitis treated successfully with antibiotics None of the patients initially treated with antibiotics that later had appendectomy had major complications The results of the APPAC trial suggest that CT proven uncomplicated acute appendicitis is not a surgical emergency and antibiotic therapy is a safe first-line treatment option Reducing unnecessary appendectomies has also been shown to lead to significant economic savings On the other hand antibiotic therapies have been shown to have an effect on the normal gut microbiota
Gut microbiota is an extremely complex ecosystem with both high bacterial density and diversity Recent scientific evidence emphasizes that the symbiosis between the host and the balanced gut microbiota supports good health and contributes to various biochemical and metabolic functions occurring in hosts body The possible role of the somehow distorted gut microbiota composition in addition to its metabolites in the etiopathogenesis of many diseases such as allergy inflammatory bowel disease type 1 diabetes and obesity related disorders has been recently proposed Further detected alterations and perturbations both in the gut microbiota composition and functionality have been linked to the development of various malignancies such as colorectal cancer gastric cancer and hepatocellular carcinoma To date the role of the microbes and especially the members of the commensal microbiota with their structural compartments and metabolites in the pathogenesis and etiology of appendicitis have not been clarified in detail despite the recent knowledge that uncomplicated acute appendicitis could be treated by antibiotic treatments alone Further there is only limited amount of evidence on the appendix microbial composition in humans
Microbial overgrowth has been speculated to serve as a secondary consequence in appendicitis However recent accumulating evidence suggests that primary bacterial infection may actually be an initiating event in the pathogenesis of the disease Interestingly it has been postulated that the appendix could serve as a microbial reservoir for repopulating the gastrointestinal tract in times of necessity thus gut microbiota may act as a source for these pathogenic intruders Further it has been reported that certain members of the gram negative Fusobacteria especially F nucleatum and necrophorum are present in most appendicitis samples
Additionally antimicrobial resistance AMR is considered an increasing global threat According to the WHO World Health Organisation in 2050s more people will be killed by AMR bacteria than by all cancersThe use of antimicrobials in humans and especially in animal health care and production industry are the major causes of increasing AMR worldwide the prudent use of antimicrobials is essential to prevent increasing AMR Antimicrobials are known to decrease the gut microbiota diversity richness and species variation and cause the perturbation of its overall balance and even a short-term antimicrobial treatment has a long-term impact on its composition underlining the importance of evaluating both short- and long-term effects of the antimicrobial treatment in old and new indications
The aims of this randomized prospective study are
1 To evaluate the possible role and differences in the microbiological etiology of complicated and uncomplicated appendicitis The bacterial composition of the complicated appendix will be compared to the gut microbiota composition determined from the fecal sample collected from the same individual Additionally these results will be compared to the gut microbiota composition of patients with uncomplicated acute appendicitis
2 To determine the effects of both antibiotic and placebo treatment on the composition of gut microbiota and to evaluate how it recovers after the appendicitis-related antimicrobial treatment AMT The bacterial composition and AMR reservoir of the gut microbiota will be evaluated both pre and post treatment in patients receiving antibiotic or placebo treatment for uncomplicated acute appendicitis Additionally the recovery of gut microbiota composition and disappearance of AMR will be evaluated We will compare two variations ivand po of antibiotic treatment with the placebo treatment
3 To evaluate the effects of the duration of the hospital stay on the AMR reservoir of the gut microbiota According to the study protocols of the APPAC II and III trials patients will spend either 1 or 3 days in the hospital in order to receive treatment before continuing the selected treatment at home We will evaluate the effects of length of stay on the AMR reservoir of gut microbiota as well as evaluating if and when possible colonization occurs
Gut microbiota is an extremely complex ecosystem with both high bacterial density and diversity Recent scientific evidence emphasizes that the symbiosis between the host and the balanced gut microbiota supports good health and contributes to various biochemical and metabolic functions occurring in hosts body The possible role of the somehow distorted gut microbiota composition in addition to its metabolites in the etiopathogenesis of many diseases such as allergy inflammatory bowel disease type 1 diabetes and obesity related disorders has been recently proposed Further detected alterations and perturbations both in the gut microbiota composition and functionality have been linked to the development of various malignancies such as colorectal cancer gastric cancer and hepatocellular carcinoma To date the role of the microbes and especially the members of the commensal microbiota with their structural compartments and metabolites in the pathogenesis and etiology of appendicitis have not been clarified in detail despite the recent knowledge that uncomplicated acute appendicitis could be treated by antibiotic treatments alone Further there is only limited amount of evidence on the appendix microbial composition in humans
Microbial overgrowth has been speculated to serve as a secondary consequence in appendicitis However recent accumulating evidence suggests that primary bacterial infection may actually be an initiating event in the pathogenesis of the disease Interestingly it has been postulated that the appendix could serve as a microbial reservoir for repopulating the gastrointestinal tract in times of necessity thus gut microbiota may act as a source for these pathogenic intruders Further it has been reported that certain members of the gram negative Fusobacteria especially F nucleatum and necrophorum are present in most appendicitis samples
Additionally antimicrobial resistance AMR is considered an increasing global threat According to the WHO World Health Organisation in 2050s more people will be killed by AMR bacteria than by all cancersThe use of antimicrobials in humans and especially in animal health care and production industry are the major causes of increasing AMR worldwide the prudent use of antimicrobials is essential to prevent increasing AMR Antimicrobials are known to decrease the gut microbiota diversity richness and species variation and cause the perturbation of its overall balance and even a short-term antimicrobial treatment has a long-term impact on its composition underlining the importance of evaluating both short- and long-term effects of the antimicrobial treatment in old and new indications
The aims of this randomized prospective study are
1 To evaluate the possible role and differences in the microbiological etiology of complicated and uncomplicated appendicitis The bacterial composition of the complicated appendix will be compared to the gut microbiota composition determined from the fecal sample collected from the same individual Additionally these results will be compared to the gut microbiota composition of patients with uncomplicated acute appendicitis
2 To determine the effects of both antibiotic and placebo treatment on the composition of gut microbiota and to evaluate how it recovers after the appendicitis-related antimicrobial treatment AMT The bacterial composition and AMR reservoir of the gut microbiota will be evaluated both pre and post treatment in patients receiving antibiotic or placebo treatment for uncomplicated acute appendicitis Additionally the recovery of gut microbiota composition and disappearance of AMR will be evaluated We will compare two variations ivand po of antibiotic treatment with the placebo treatment
3 To evaluate the effects of the duration of the hospital stay on the AMR reservoir of the gut microbiota According to the study protocols of the APPAC II and III trials patients will spend either 1 or 3 days in the hospital in order to receive treatment before continuing the selected treatment at home We will evaluate the effects of length of stay on the AMR reservoir of gut microbiota as well as evaluating if and when possible colonization occurs
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None