| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| We wish to investigate if intraoperative intraperitoneal administration of fosfomycin, metronidazole and rhGM-CSF followed by oral antibiotic for three days is as effective as the current intravenous antibiotic treatment given during and three days after appendectomy for perforated appendicitis. |
| Vi ønsker at undersøge om intraperitoneal indgivelse af fosfomycin, metronidazol og rhGM-CSF efterfulgt af tabletbehandling med antibiotika i tre dage er lige så effektivt som det aktuelle standardbehandling med intravenøs antibiotika givet under og efter appendektomi for perforeret appendicitis. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Antibiotics agents administered into the abdominal cavity. compared with antibiotic agents administrated intravenously for perforated appendicitis. |
| Antibiotika i bughulen sammenlignet med antibiotika i blodet til behandling af blindtarmsbetændelse med hul |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10000680 |
| E.1.2 | Term | Acute appendicitis without mention of peritonitis |
| E.1.2 | System Organ Class | 100000004862 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary outcome is the total length of hospital stay, defined as the number of hours in hospital after end of operation (not before operation) and until 30-day follow-up. |
|
| E.2.2 | Secondary objectives of the trial |
| Secondary outcomes include Gastrointestinal Quality of Life Index (GIQLI), postoperative complications according to the Clavien-Dindo grading, surgical site infections requiring surgical drainage, intraabdominal abscesses requiring drainage, readmissions, reoperations, time to return to normal activities, period of sick leave “absence from work”, and costs. All are measured up to 30 days postoperatively. Further, if an infectious complication occurs, investigations of the specimens’ microbiological flora including susceptibility testing for the antibiotics used for treatment will be undertaken. Side effects will be monitored through a questionnaire. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Age ≥18 years
Suspicion of acute appendicitis and planned for diagnostic laparoscopy and eventual laparoscopic appendectomy
Perforated appendicitis (diagnosed during surgery by the surgeon)
Negative p-HCG (women)
Written informed consent after written and verbal information (preoperatively at Herlev Hospital and postoperatively at Bispebjerg Hospital) |
Alder≥18 år
Mistænkt syg af en blindtarmsbetændelse og planlagt til en kikkertoperation med henblik på at fjerne blindtarmen
Blindtarmsbetændelse med synligt hul (diagnosticeret under operationen)
Negativ graviditetstest (kvinder)
Skriftligt, informeret samtykke efter mundtlig og skriftlig information (før operationen på Herlev Hospital og efter operationen på Bispebjerg Hospital) |
|
| E.4 | Principal exclusion criteria |
Cannot understand, read or speak Danish
Previous allergic reaction to fosfomycin, metronidazole, rhGM-CSF, or penicillins e.g. piperacillin or amoxicillin
Diagnostic laparoscopy revealing normal appendix not requiring an appendectomy or appendicitis without perforation
Other intra-abdominal pathology requiring surgical intervention at the same operation
Known renal or hepatic disease or biochemical evidence at the time of admission
Known hematologic disease in current medical treatment
American Society of Anesthesiologists (ASA) physical status ≥4 (a patient with severe systemic disease that is a constant threat to life)
Body weight >110 kg
Surgery converted to open appendectomy
Anticipated compliance problems |
Ikke i stand til at forstå, læse eller tale dansk
Tidligere allergisk reaktion overfor fosfomycin, metronidazol, granulocyt-makrofag koloni-stimulerende faktor eller penicilliner eks. piperacillin eller amoxicillin
Ikke nødvendigt at fjerne blindtarmen under kikkertoperationen eller blindtarmsbetændelse uden hul
Anden operationskrævende sygdom i bughulen under operationen
Kendt med nyre- eller leversygdom
Kendt med blodsygdom, der kræver medicinsk behandling
American Society of Anaesthesiologists (ASA)≥4 (en patient med svær systemisk sygdom, som er en konstant trussel mod livet)
Vægt >110 kg
Operation konverteret til åben operation for blindtarmsbetændelse
Ikke i stand til at gennemføre forsøgets målepunkter af andre årsager |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Total length of in hospital stay (measured in hours) is defined as from end of the operation until discharge from the hospital plus length of stay during a possible readmission within 30 days from surgery. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| This will be calculated at the patient’s record review 30 days postoperatively (±3 days). |
|
| E.5.2 | Secondary end point(s) |
GIQLI: a disease-specific questionnaire validated in Danish is collected at 10 days postoperatively (±2 day) and at 30 days postoperatively (±3 days).
Postoperative complications: according to the Clavien-Dindo grading: information regarding complications is collected after surgery during hospital stay, 10 days postoperatively (±2 day) when the patients have their sutures removed by the trial personnel and 30 days (±3 days) postoperatively through review of the patients’ medical records and by the planned telephone interview.
Deep surgical site infection postoperatively: Information regarding surgical site infections is collected 10 days postoperatively (±2 day) when the patients have their sutures removed by the trial personnel and 30 days (±3 days) postoperatively through review of the patient’s medical records and at the planned telephone call to the patients. It is defined as deep incisional surgical site infection according to Centre for Disease Control and Prevention (CDC).
Intraabdominal abscess: Information regarding intraabdominal abscesses is collected 10 days postoperatively (±2 day) when the patients have their sutures removed by the trial personnel and 30 days (±3 days) postoperatively through review of the patient’s medical records and at the planned telephone interview. It is defined as an organ/space surgical site infection according to CDC. If a collection is found but not drained, it is not regarded as an abscess by definition in the current trial.
Readmissions: Information will be collected 30 days (±3 days) postoperatively by review of the patient’s medical records and at the planned telephone interview. Only readmissions related to the surgery will be registered; e.g. admission and treatment of a non-related condition will not be registered.
Reoperations: Information will be collected 30 days (±3 days) postoperatively by review of the patient’s medical records and at the planned telephone interview.
Time to return to normal activities: This time point will be determined either 10 days (±2 days) postoperatively when the patients have their sutures removed by the trial personnel or 30 days (±3 days) postoperatively through the planned telephone interview of the participants. The date is defined at the time point at which the participant could return to normal daily activities.
Period of sick leave (absence from work): This time point will be determined either 10 days (±2 days) postoperatively when the patients have their sutures removed by the trial personnel or 30 days (±3 days) postoperatively through the planned telephone interview of the participants. The parameter is defined as the number of days from the operation to the time point at where the participant returned to work or school.
Microbiological flora and susceptibility: Participants with suspicion of postoperative infectious complication will typically have specimens collected at the infectious site. This will either be swabs from the surgical site (in case of surgical site infection) or pus (in case of intraabdominal abscesses). If organisms consistent with infections of the respective type are isolated, the participant is defined as having an infectious complication. If neither surgical intervention (drainage procedure) nor simple specimen collection has been performed, then there is not an infectious complication by definition. This covers potential infectious complications at the surgical wounds or an intraabdominal abscess. Thus, pneumonia will be regarded as an infectious complication if only treated by antibiotics but without specimen collection.
Adverse events: registered by trial personnel during admission, 10 days (±2 days) postoperatively when the patients have their sutures removed by the trial personnel and 30 days (±3 days) postoperatively through review of the patient’s medical records and at the planned telephone call to the patients.
Side effects: A questionnaire regarding side effects will be filled out by the patients. Questions about side effects will be evaluated at the first, postoperative day and 10 days (±2 days) postoperatively when the patients have their sutures removed by the trial personnel.
Costs: The estimated total costs of admission, surgery, possible complications, reoperations etc. in the two treatment groups. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | No |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
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