Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT03257423 |
| Other study ID # |
MAPPAC |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 4, 2017 |
| Est. completion date |
December 31, 2025 |
Study information
| Verified date |
November 2020 |
| Source |
Turku University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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 host's 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 cancers.The 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 (i.v.and p.o.) 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.
