To generate high quality empirical evidence for the effectiveness in terms of proportion of patients experiencing complications, quality of life and costs of initial non-operative treatment strategy (reserving appendectomies for those not responding…
ID
Source
Brief title
Condition
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary (patient level): The proportion of patients experiencing complications
within one year-follow up. An adjudication committee will be installed to
review the complications.
Complications are defined as:
• Allergic reaction to antibiotics administered. In case an allergic reaction
is suspected, the child will be referred to the
allergist for further evaluation.
• Re-admission for an indication other than recurrent appendicitis but related
to appendicitis (such as readmission for
observation of fever or abdominal pain)
• Complications associated with appendectomy:
- Superficial Site infection
- Intra-abdominal abscess
- Stump leakage/stump appendicitis
- Secondary / prolonged Bowel Obstruction
- Anesthesia Related complications (such us pneumonia)
- Hernia cicatricalis
- Need for other surgical or radiological intervention than appendectomy but
related to appendicitis (such as percutaneous
drainage of an abscess, surgical intervention for a superficial site infection)
Secondary outcome
Number of days absent from school, social or sport events (patient-level)
Number of days absent from work (parents-level)
Total number of extra visits (not the already scheduled ones) to the outpatient
clinic, general practitioners office or emergency department for abdominal
pain.
Total length of hospital stay during the follow-up period for strategy related
treatment or complications (An adjudication committee will be installed to
review the length of hospital stay)
Total days of analgesics medication use
Proportion of patients with missed diagnosis of complex appendicitis with risk
of peritonitis
Proportion of patients not having to undergone appendectomy
Proportion of patients experiencing recurrent appendicitis within one-year
follow-up.
Recurrent appendicitis is defined as those patients with a clinical and
radiological high suspicion of recurrent appendicitis who undergo an
appendectomy and histopathological examination confirms the diagnosis of
recurrent appendicitis
Proportion of patients experiencing early failure of initial non-operative
treatment.
Early failure is defined as all patients that undergo an appendectomy during
the antibiotic course (iv or oral) due to persistent complaints, clinical
deterioration or faecolith.
Proportion of patients that undergo interval appendectomy.
Interval appendectomy is defined as those patients that undergo an appendectomy
with a clinical and radiological low suspicion of recurrent appendicitis.
Histopathological examination shows no signs of recurrent appendicitis.
Quality of life measured by the validated CHQ-CF87, EQ-5d-Youth and EQ-5d-Proxy
questionnaire.
Medical, non-medical and indirect costs at one year follow up of the treatment
strategy (iMCQ and iPCQ, adjusted to the situation of child and parents)
QALY*s
Patient satisfaction measured by the NET PROMOTOR SCORE en validated Patient
Satisfaction Questionnaire (PSQ)18.
Factors associated with implementability
Background summary
Initial non-operative treatment of acute simple appendicitis has recently been
investigated in both the adult as the paediatric population. In the adult
population, six RCTs showed that an appendectomy could be avoided in 40-76% of
the patients at the end of their follow-up period. Despite the fact that some
patients need to undergo a delayed appendectomy, it has been demonstrated in
systematic reviews that non-operative treatment strategy is associated with a
significant reduction in complications, faster recovery and return to work,
less pain duration and analgesic medication consumption. In children only pilot
data is yet available. Short-term success rates of this strategy (including of
our own pilot cohort study) are between the 83-92%. Long-term results (one-year
follow-up) are available from two studies; 62-75% did not require an
appendectomy. No large RCT have yet been conducted in the paediatric
population. It is therefore essential to generate high quality empirical
evidence regarding this strategy in this subset of patients.
Study objective
To generate high quality empirical evidence for the effectiveness in terms of
proportion of patients experiencing complications, quality of life and costs of
initial non-operative treatment strategy (reserving appendectomies for those
not responding or with recurrent disease), compared with appendectomy strategy
in children, 7 and 17 years old, with acute simple appendicitis.
Study design
A national unblinded multi-centre non-inferiority randomized controlled trial
with a 1:1 block randomization stratified by hospital will be performed.
(academic en non-academic)
Intervention
Intervention group (Non-operative treatment strategy): Clinical observation for
48 hours with administration of 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 for 48 hours. If
after 48 hours the patient fulfils the predefined discharge criteria, 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 and discharge. An
appendectomy is reserved for those patients with clinical deterioration,
non-improvement after 72 hours or recurrent appendicitis.
Control group (Operative treatment strategy): Clinical observation and
semi-urgent appendectomy. Pre-, peri- and postoperative care according to local
protocol. No routine postoperative antibiotics. Discharge if the patient
fulfils the predefined discharge criteria.
Study burden and risks
1. Risks of participation:
- Specific non-operative treatment strategy: possible need for delayed
operation (10-25%), recurrent appendicitis (10%).
- Both strategies: Allergic reaction to antibiotics (<1%), known appendectomy
associated complications (5-10%).
2. Burden of participation:
- Specific non-operative treatment strategy: Extra admission day (in comparison
with appendectomy), ultrasonography after 48 hours (extra non-invasive
procedure), Blood samples after 24 and 48 hours for determination of C-reactive
protein / Leucocytes (2x extra a 1 cc). Blood samples will be obtained through
the already placed IV access. In case this is not successful, an extra
venapunction will be performed.
- Both strategies:
• Telephone interviews/Email (3x5minutes=15 minutes).
* Filling out questionnaires (1x only QOL, 4x QOL, iMCQ and iPCQ, adjusted to
the situation of child and parents
, PSQ-18, net promotor scale). Duration of filling out questionnaires:
QOL: 10 minutes (5x10=50 minutes)
iMCQ and iPCQ: 10 minutes (3x10=30 minutes)
PSQ/Net premotor scale: 5 minutes (4x5=20 minutes)
Total time per participant in one year follow up: 100 minutes
3.Benefit of non-operative treatment strategy: Avoidance of surgery (75-90%)
and its related early and late morbidity, potential better quality of life.
The risk and burden are minimised although in order to improve safety, some
extra procedures are necessary.
External monitoring and a DMC will be installed in order to improve patient
safety.
Meibergdreef Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Eligible for inclusion are all children from 7 to 17 years old, inclusive, with
a radiologically confirmed simple appendicitis. Definition of simple
appendicitis is based upon predefined clinical, biochemical and radiological
(ultrasound) criteria.
Clinical & biochemical criteria:
- Unwell but not generally ill
- Localized tenderness in the right iliac fossa region
- Normal/hyperactive bowel sounds
- No guarding or palpable mass
- Biochemical signs of infection (Elevated White Blood Cell count (WBC) and/or
C-reactive protein (CRP)).
As recommended by the national guideline, all children with a clinical and/or
biochemical suspicion should undergo ultrasound studies. Ultrasound criteria to
confirm the diagnosis of acute simple appendicitis are:
- An incompressible, painful appendix with an outer diameter > 6 mm
- Secondary signs of inflammation such as surrounding fat infiltration, limited
clear free fluid surrounding the appendix, hyperemia within the appendiceal
wall.
- No fecolith, no signs of perforation, no signs of intra-abdominal abscess or
phlegmone.
In case the ultrasound is inconclusive, additional imaging studies may be
obtained. CT-scan is not recommended in the young children (due to its risk of
radiation induced malignancy). MRI is recommended in those places with
sufficient experience in the interpretation of the results. Only those in whom
imaging studies confirm the diagnosis of simple appendicitis can be included.
In case there is no certain diagnosis and a *watchful waiting* strategy is
chosen, the patient cannot be included.
Exclusion criteria
Exclusion criteria:
• Generalized peritonitis, complex appendicitis or sepsis (based upon
predefined criteria and scoring system).
Scoring system: As scoring system was developed determining the risk of
complex appendicitis based upon five pre-operative variable. Points have been
awarded to each variable. In case the total score is less than 4 points, the
patient is likely to have a simple appendicitis. In case the score is 4 or more
points, the chance of having complex appendicitis is significant and those
children will be excluded from this study. Variables:
Diffuse abdominal guarding (3 points)
CRP level more than 38 mg/L (2 points)
Signs on ultrasound indicative of complex appendicitis (2 points)
More than one day abdominal pain (2 points)
Temperature: more than 37.5 degree Celsius (1 point)
• Fecolith (ultrasound)
• Serious co-morbidity
• Recurrent appendicitis
• Suspicion of an underlying malignancy or inflammatory bowel disease
• Documented type 1 allergy to the antibiotics used.
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-003052-70-NL |
| ClinicalTrials.gov | NCT02848820 |
| CCMO | NL56792.018.16 |