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Acute Appendicitis and Microbiota - Etiology of Appendicitis and Antibiotic Therapy Effects (MAPPAC)

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ClinicalTrials.gov Identifier: NCT03257423
Recruitment Status : Unknown
Verified August 2017 by Paulina Salminen, Turku University Hospital.
Recruitment status was:  Enrolling by invitation
First Posted : August 22, 2017
Last Update Posted : August 22, 2017
Sponsor:
Collaborators:
Tampere University Hospital
Oulu University Hospital
Kuopio University Hospital
Helsinki University Central Hospital
Jyväskylä Central Hospital
Information provided by (Responsible Party):
Paulina Salminen, Turku University Hospital

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.

Condition or disease Intervention/treatment Phase
Acute Appendicitis Drug: Ertapenem followed by levofloxacin and metronidazole Drug: Moxifloxacin Procedure: Appendectomy Other: Placebo Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients are enrolled in conjuction with APPAC II (NCT03236961) and APPAC III (NCT 03234296) trials, all patients with uncomplicated or complicated acute appendicitis are evaluated for MAPPAC enrollment. MAPPAC study groups: complicated acute appendicitis (samples: rectal swabs, serum, removed appendix), APPAC II patients in two groups according to APPAC II randomized antibiotic therapy (uncomplicated acute appendicitis, samples: rectal swabs, serum and in cases of antibiotic treatment failure or appendicitis recurrence also removed appendix), APPAC III patients in two groups according to APPAC III randomized group of antibiotc or placebo therapy (uncomplicated acute appendicitis, samples: rectal swabs, serum and in cases of antibiotic or placebo treatment failure or appendicitis recurrence also removed appendix), and patients with uncomplicated acute appendicitis declining to participate in APPAC II or III trials undergoing appendectomy
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Acute Appendicitis and Microbiota - Ethology of Appendicitis and Effects of the Antimicrobial Treatment - The MAPPAC (Microbiology Appendicitis Acuta) Trial
Actual Study Start Date : April 4, 2017
Estimated Primary Completion Date : April 4, 2019
Estimated Study Completion Date : April 4, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: I.v. + p.o. antibiotics (APPAC II)
Patients in this group recruited also in APPAC II trial will receive i.v. antibiotics (ertapenem 1 g twice per day) for 2 days followed by p.o. antibiotics (levofloxacin 500 mg x 1 and metronidazole 500 mg x 3) for 5 days, for a total treatment duration of 7 days. From these patients, rectal swab samples will be collected at day 0 (before treatment) and day 1 (after beginning of treatment), serum sample before treatment initiation.
Drug: Ertapenem followed by levofloxacin and metronidazole
Ertapenem 1 g i.v. daily for either 2 days (MAPPAC + APPAC II patients) or 3 days (MAPPAC + APPAC III) followed by p.o. levofloxacin 500 mg x 1 + metronidazole 500 mg x 3 for either 5 days (APPAC II + MAPPAC) or 4 days (APPAC III + MAPPAC)

Active Comparator: P.o. moxifloxacin (APPAC II)
Patients in this group recruited also in APPAC II trial will receive p.o. antibiotics for a total of 7 days, moxifloxacin 400 mg once per day. From these patients, rectal swab samples of faces will be collected at two time points, day 0 (before treatment) and day 1 (after beginning of treatment), serum sample before treatment initiation.
Drug: Moxifloxacin
Moxifloxacin 400 mg once a day for seven days (APPAC II + MAPPAC)

Placebo Comparator: Placebo treatment (APPAC III)
Patients in this group recruited also in APPAC III trial will receive i.v. placebo 3 times per day for 3 days followed by p.o. placebo 3 times per day for 4 additional days. From these patients rectal swab samples will be collected twice during the stay at the research hospital (time points 0 and 1 or 3 d) and three times at home (follow-up at one week, six months and one year). Serum samples are taken prior to treatment initiation and at 10 days after the treatment initiation.
Other: Placebo
Placebo i.v. once a day for three days (APPAC III + MAPPAC) followed by placebo capsules three times a day for four days.

Surgery (complicated appendicitis)
Patients in this group will undergo appendectomy and are recruited only in the MAPPAC trial. Rectal swab samples and biopsies from the removed appendix will be collected from these patients.
Procedure: Appendectomy
Primarily laparoscopic appendectomy for either complicated acute appendicitis or uncomplicated acute appendicitis (refusing to participate in APPAC II or III trials or recurrent acute appendicitis).

Surgery (uncomplicated appendicitis)
Patients in this group will undergo appendectomy either after refusing to participate in the APPAC II or APPAC III trials or after presenting with recurrent appendicitis after antibiotic or placebo therapy. Rectal swab samples of faces and biopsies from the removed appendix will be collected from these patients.
Procedure: Appendectomy
Primarily laparoscopic appendectomy for either complicated acute appendicitis or uncomplicated acute appendicitis (refusing to participate in APPAC II or III trials or recurrent acute appendicitis).

Active Comparator: I.v. + p.o. antibiotics (APPAC III)
Patients in this group recruited also in APPAC III trial will receive i.v. antibiotics (ertapenem 1 g twice per day) for 3 days followed by p.o. antibiotics (levofloxacin 500 mg x 1 and metronidazole 500 mg x 3) for 4 days, for a total treatment duration of 7 days. From these patients rectal swab samples will be collected twice during the stay at the research hospital (time points 0 and 1 or 3 d) and three times at home (follow-up at one week, six months and one year). Serum samples are taken prior to treatment initiation and at 10 days after the treatment initiation.
Drug: Ertapenem followed by levofloxacin and metronidazole
Ertapenem 1 g i.v. daily for either 2 days (MAPPAC + APPAC II patients) or 3 days (MAPPAC + APPAC III) followed by p.o. levofloxacin 500 mg x 1 + metronidazole 500 mg x 3 for either 5 days (APPAC II + MAPPAC) or 4 days (APPAC III + MAPPAC)




Primary Outcome Measures :
  1. Microbiology in the etiology of acute appendicitis [ Time Frame: 1 day ]
    Differences in the microbiological etiology of complicated and uncomplicated appendicitis


Secondary Outcome Measures :
  1. Effects of antimicrobial treatment on gut microbiota [ Time Frame: 1 year ]
    Determining 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 evaluated by rectal swabs pre- and post treatment

  2. Effects of hospital stay duration on the AMR reservoir of the gut microbiota [ Time Frame: 3 days ]
    The effect of length of hospital stay (days) on the AMR reservoir of gut microbiota and colonization occurrence evaluated by analysing rectal swabs microbiota pre- and post-treatment at 0, 1 and 3 days.



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18-60 years
  • CT confirmed uncomplicated or complicated acute appendicitis
  • Ability to give consent to participate in the study

Exclusion Criteria:

  • Age under 18 years or over 60 years
  • Pregnancy or lactation
  • Allergy to contrast media or iodine
  • Allergy or contraindication to antibiotic therapy
  • Renal insufficiency
  • Metformin medication
  • Severe systemic illness (for example malignancy, medical condition requiring immunosuppressant medication)
  • Inability to co-operate and give informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03257423


Locations
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Finland
Turku University Hospital
Turku, Finland
Sponsors and Collaborators
Turku University Hospital
Tampere University Hospital
Oulu University Hospital
Kuopio University Hospital
Helsinki University Central Hospital
Jyväskylä Central Hospital
Investigators
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Principal Investigator: Paulina Salminen, MD, PhD Turku University Hospital

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Responsible Party: Paulina Salminen, MD, PhD, Chief of Acute Care Surgery, Turku University Hospital
ClinicalTrials.gov Identifier: NCT03257423     History of Changes
Other Study ID Numbers: MAPPAC
First Posted: August 22, 2017    Key Record Dates
Last Update Posted: August 22, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Paulina Salminen, Turku University Hospital:
Uncomplicated acute appendicitis
Complicated acute appendicitis
Antibiotic therapy
Microbiological etiology
Additional relevant MeSH terms:
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Appendicitis
Acute Disease
Intraabdominal Infections
Infection
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Cecal Diseases
Intestinal Diseases
Disease Attributes
Pathologic Processes
Anti-Bacterial Agents
Moxifloxacin
Metronidazole
Levofloxacin
Ofloxacin
Ertapenem
Antibiotics, Antitubercular
Norgestimate, ethinyl estradiol drug combination
Anti-Infective Agents
Antitubercular Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents