Antibiotica voor de behandeling van acute blindedarmontsteking bij kinderen.|
|- candidate number||9242|
|- NTR Number||NTR2810|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||15-mrt-2011|
|- Secondary IDs||KCA2011 Kinderchirurgisch Centrum Amsterdam|
|- Public Title||Antibiotica voor de behandeling van acute blindedarmontsteking bij kinderen.|
|- Scientific Title||Antibiotic treatment alone for acute simple appendicitis in children; a pilot study part of the APAC trial.|
|- Healt Condition(s) or Problem(s) studied||Children, Appendicitis, Antibiotics|
|- Inclusion criteria||1. Informed consent;|
2. Children 4-17;
3. Radiological conformed simple appendicitis (non perforated).
|- Exclusion criteria||1. Generalized peritonitis;|
2. Severe sepsis or septic shock;
3. Serious associated co morbidity (heart, malignancy, pulmonary, immunodeficiency);
4. Documented type 1 allergy to antibiotics used.
|- mec approval received||no|
|- multicenter trial||yes|
|- Type||Single arm|
|- planned startdate ||1-jun-2011|
|- planned closingdate||1-jun-2013|
|- Target number of participants||50|
|- Interventions||Intravenous amoxicillin/clavulanic acid + gentamicin. Amoxicillin/clavulanic acid will be given 4 times a day 100/10 mg/kg and gentamicin once a day 7 mg/kg. |
|- Primary outcome||1. Failure of antibiotic treatment alone;|
2. Percentage of patients willing to participate.
|- Secondary outcome||1. Number of days with abdominal pain;|
2. Duration of hospital stay;
3. Time to resume normal activities;
4. Days of antibiotic use;
5. Time to adequate caloric oral intake.
|- Timepoints||1. Short term (1 month);|
2. Long term (1 year).
A QOLquestionaire will be used for measurements.
|- Trial web site||N/A|
|- status||stopped: trial finished|
|- CONTACT FOR PUBLIC QUERIES||Drs. R.R. Gorter|
|- CONTACT for SCIENTIFIC QUERIES||Drs. R.R. Gorter|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|VU University Medical Center|
|- Brief summary||Appendectomy for acute appendicitis has been recently questioned as being the only correct treatment for appendicitis. Two clinical trials in selected patients (males older than 18 years) comparing appendectomy and antibiotic treatment alone as primary mode of treatment found that antibiotic treatment alone is safe and effective in 85 % of the patients, in addition appendectomy has been reported to have significant early and late morbidity. This can be avoided with antibiotic treatment alone. Moreover better quality of life and lower costs have been associated with antibiotic treatment alone. Conclusive evidence with regard to the effectiveness and cost-effectiveness of antibiotic treatment alone in selected cases with proven acute appendicitis in children however is lacking. Our pilot study will determine if antibiotic treatment alone is safe and effective and if a non inferiority trial (APAC) is currently feasible.|
|- Main changes (audit trail)||Rationale: |
In the Netherlands, approximately 16,000 appendectomies are performed each year. In the past, the fear of a perforation of the appendix leading to peritonitis was the justification of aggressive therapy; appendectomy even in the middle of the night. Nowadays, it appears that not all appendicitis will progress to a perforation over time; rather it seems that two types of appendicitis exist: Simple (non-perforating) and Complex (perforating). Therefore the treatment of appendicitis in adults has become subject of debate. Recent studies in adults with appendicitis have reported an effective antibiotic treatment alone in up to 2/3 of the patients; reserving appendectomy for those not improving with antibiotics. Although appendectomy is an effective method to treat appendicitis, it is also associated with significant early and late morbidity such as intra-abdominal abscess formation, wound-infection, anaesthesia related risks, etcetera. Conclusive evidence with regard to the efficacy of antibiotic treatment alone in children with proven acute appendicitis however is lacking. We propose a prospective cohort study to answer the following questions:
1. Is a non inferiority randomised controlled trial to determine the effectiveness and safety of antibiotic treatment alone versus appendectomy in children aged 7-17 with proven appendicitis (simple and complex) feasible?
2. Is antibiotic treatment alone for simple appendicitis in children aged 7-17 years safe?
Prospective multi centre pilot cohort study.
Children (7-17years old) with radiological proven simple appendicitis.
Intravenous administration of amoxicillin/clavulanic acid 25/2.5mg 6-hourly (total 100/10 mg/kg daily) and gentamicin 7mg/kg once daily will be given for 48 hours. If possible the antibiotics will be switched to oral amoxicillin/clavulanic acid 50/12.5 mg/kg 8-hourly. Total duration of treatment (IV + oral) is 7 days. If after 72 hours, the patient does not meet the predefined criteria, an appendectomy will be performed.
Main study parameters/endpoints:
1. Number of patients willing to participate in this study, defined as signed informed consent / number of patients eligible for inclusion.
2. Safety of antibiotic treatment defined as:
a. Failure of antibiotic treatment alone defined as:
Need for secondary operation due to lack of response to antibiotic treatment
b. Occurrence of major complications defined as anaphylactic shock and other allergic reaction to antibiotics administered
c. Recurrent appendicitis within 8 weeks
d. Recurrent appendicitis within one year after discharge
e. Occurrence of major complaints after secondary appendectomy
Inclusion period September 2012 t/m September 2014 (Total of 50 participants)
Follow up 2, 8 and 52 weeks.
Appendectomy for acute appendicitis has recently been questioned as being the only correct treatment for appendicitis. Appendectomy has been reported to have significant early and late morbidity. This can be avoided with antibiotic treatment alone. Moreover, better quality of life and lower costs have been associated with antibiotic treatment alone. Five clinical trials in selected patients (males, older than 18 years) comparing appendectomy and antibiotic treatment alone as primary mode of treatment found that antibiotic treatment alone is safe and effective in 48-95% of the patients Conclusive evidence with regard to the efficacy of antibiotic treatment alone in children with proven acute appendicitis however is lacking. We propose a prospective cohort study to answer the following questions:
Primary research question:
What is the complication rate of the initial antibiotic treatment strategy (IATS) for acute simple appendicitis (radiological proven) in children aged 7-17 years old?
Secondary research question:
What is the complication rate of the direct appendectomy treatment strategy (DATS) for acute simple appendicitis (radiological proven) in children aged 7-17 years old?
Multi-centre prospective cohort study.
Children (7-17years old) with radiologically proven simple appendicitis.
• Age 7-17 years
• Radiologically confirmed simple appendicitis, defined as:
a. Clinical findings:
i. Unwell, but not generally ill
ii. Localized tenderness in the right iliac fossa region
iii. Normal/hyperactive bowel sounds
iv. No guarding
v. No mass palpable
b. Ultrasonography (see appendix 13.13):
i. Incompressible appendix with an outer diameter of ≥6 mm
ii. Hyperaemia within the appendiceal wall
iii. Without faecolith
iv. Infiltration of surrounding fat
v. No signs of perforation
vi. No signs of intra-abdominal abscess/phlegmone
1. Patients with severe general illness at time of presentation:
a. Generalized peritonitis defined as:
Diffuse inflammation of the peritoneum with clinical signs consisting of increasing abdominal pain, generalized tenderness, diffuse abdominal rigidity, sinus tachycardia, signs of paralytic ileus
b. Severe sepsis or septic shock, as defined by the international paediatric sepsis consensus conference . (appendix 13.6)
c. Signs of complex appendicitis
2. Children with a faecolith on ultrasonography.
3. Patients with serious associated conditions or malformations such as:
a. Congenital or acquired cardiac or pulmonary disease with significant hemodynamic consequences
d. Homozygous sickle cell disease
e. Metabolic disorders
4. Patient with documented type 1 allergy to the antibiotics used
Initial antibiotic treatment strategy (IATS): Intravenous administration of amoxicillin/clavulanic acid 25/2.5mg 6-hourly (total 100/10 mg/kg daily; maximum 6000/600mg a day) and gentamicin 7mg/kg once daily will be given for 48 hours. If possible the antibiotics will be switched to oral amoxicillin/clavulanic acid 50/12.5 mg/kg 8-hourly (max 1500/375mg a day) for in total 7 days. If after 72 hours, the patient does not meet the predefined criteria, an appendectomy will be performed.
The control group will consist of patients, who do not want the antibiotic treatment. Their medical files will be monitored prospectively. In addition they will be scheduled for an extra outpatient clinic follow up (8 weeks after discharge), extra telephone contact one year after discharge and asked to fill out quality of life questionnaires.
Safety of initial antibiotic treatment defined as:
Occurrence of major complications, such as:
A. Anaphylactic shock and other allergic reaction to antibiotics administered
b. Recurrent appendicitis within 8 weeks
c. Recurrent appendicitis within one year after discharge
d. Development of perforated appendicitis
e. Occurrence of major complaints after delayed appendectomy such as intra-abdominal abscess (IAA), stumpleakage, superficial site infection (SSI), anaesthesia related complications, secondary bowel obstruction (SBO), re-admission, need for re-intervention
g. Re-intervention other than delayed appendectomy
Secondary outcome parameters
Major complications associated with appendectomy
b. Intra-abdominal abscess (IAA)
c. Secondary bowel obstruction (SBO)
d. Superficial site infection (SSI)
e. Need for secondary operation
f. Need for other re-intervention
h. Anaesthesia related complication
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
1. Risks of participation: Need for delayed operation, recurrent appendicitis. Risks that are also present in case of non-participation: Allergic reaction to antibiotics, known appendectomy associated complications.
2. Burden of participation: Extra admission day (in comparison with appendectomy), ultrasonography after 48 hours (extra procedure), outpatient follow up (two extra visits), filling out QOL questionnaires. Burden also present in case of non-participation: Intravenous access (normal procedure), daily blood samples (normal procedure). Regarding the control group, the burden will consist of an extra outpatient clinic follow up (8 weeks after discharge), extra telephone contact one year after discharge and fill out quality of life questionnaires.
3. Benefit of participation: Avoidance of surgery and its related early and late morbidity, potential better quality of life.
|- RECORD||15-mrt-2011 - 7-feb-2017|
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