Clinical Trial Results:
Optimized treatment for uncomplicated acute appendicitis - active observation with or without antibiotic treatment. A phase IV consecutive clinical treatment trial.
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Summary
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EudraCT number |
2018-001578-71 |
Trial protocol |
SE |
Global end of trial date |
30 Jun 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
16 Feb 2025
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First version publication date |
16 Feb 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
App2018 V2
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03985514 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Göteborgs Universitet
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Sponsor organisation address |
Sahlgrenska Universtetssjukhuset/Kirurgi, Göteborg, Sweden, 41345
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Public contact |
Department of Surgery, Sahlgrenska Universtiy hospital, Göteborgs Universitet, kent.lundholm@surgery.gu.se
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Scientific contact |
Department of Surgery , Sahlgrenska University Hospital, Göteborgs Universitet, kent.lundholm@surgery.gu.se
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Dec 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Jun 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Antibiotic treatment to unselected patients with acute appendicitis is safe and effective. However, it is unknown to what extent early provision of antibiotic treatment may represent over-treatment due to spontaneous healing of appendix inflammation. The aim of the present study was to evaluate the role of antibiotic treatment versus active in-hospital observation on spontaneous regression of acute appendicitis.
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Protection of trial subjects |
The study compares two options for conservative treatment of appendicitis, both of which are approved treatment options in Swedish healthcare.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 May 2018
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Scientific research | ||
Long term follow-up duration |
12 Months | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Sweden: 126
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Worldwide total number of subjects |
126
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EEA total number of subjects |
126
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
126
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Persons who requested acute medical care at Sahlgrenska University hospital and presented clinical sympoms of acute appendicits were screened according to inclusion/exclusion criteria. Patients who accepted participation in the study were included and allocated to treatment group by block-randomization. | |||||||||
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Pre-assignment
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Screening details |
Patients presenting with symptoms of clinical acute appendicitis and fulfilling inclusion criteria. Age 18-60 years. Leucocyte blood count < 13,000 µL C-reactive protein < 60 mg/L | |||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
The study is a block-randomised study with block alternatives for treatments decided before inclusion.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Study group | |||||||||
Arm description |
Active observation with addition of antibiotic treatment. Antibiotics were administered as in-hospital intravenous infusion (24-48 hours) followed by 7-10 days out-hospital oral ab. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Piperacillin/Tazobactam
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Investigational medicinal product code |
ATC code: J01CR05
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for concentrate for solution for infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Piperacillin/Tazobactam (4 g/0.5 g) in 8 -hour intervals, principally attempted for at least 24 hours.
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Investigational medicinal product name |
Ciprofloxacin
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Investigational medicinal product code |
ATC code: J01MA2
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Other name |
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Pharmaceutical forms |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
0.5 g twice daily for 7-10 days.
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Investigational medicinal product name |
Metronidazole
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Investigational medicinal product code |
ATC code: P01AB01
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Other name |
Flagyl
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
400 mg tree times daily for 7-10 days.
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Arm title
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Control group | |||||||||
Arm description |
Active inhospital observation according to standard of care. | |||||||||
Arm type |
No intervention | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Study group
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Reporting group description |
Active observation with addition of antibiotic treatment. Antibiotics were administered as in-hospital intravenous infusion (24-48 hours) followed by 7-10 days out-hospital oral ab. | ||||||||||||||||||||||||||||||||||||
Reporting group title |
Control group
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Reporting group description |
Active inhospital observation according to standard of care. | ||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Study group
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Reporting group description |
Active observation with addition of antibiotic treatment. Antibiotics were administered as in-hospital intravenous infusion (24-48 hours) followed by 7-10 days out-hospital oral ab. | ||
Reporting group title |
Control group
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Reporting group description |
Active inhospital observation according to standard of care. | ||
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End point title |
Treatment failure (need of acute appendectomy) | |||||||||
End point description |
Final proportion of patients in each group that needed acute appendectomy, despite inital observation or observation+ antibiotics.
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End point type |
Primary
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End point timeframe |
From inclusion to discharge from hospital at initial hospital stay. Information on recurrence rates for entire study period (2018-2021) are reported in the publication. Life-table analysis indicated a 38% benefit for the antibiotic group.
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Statistical analysis title |
Operation at inital hospital stay | |||||||||
Comparison groups |
Study group v Control group
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Number of subjects included in analysis |
126
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
< 0.005 | |||||||||
Method |
Chi-squared | |||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
From administration to hospital discharge.
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Assessment type |
Systematic | ||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||
Dictionary version |
10.0
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Reporting groups
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Reporting group title |
Study group
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Reporting group description |
Active observation with addition of antibiotic treatment. Antibiotics were administered as in-hospital intravenous infusion (24-48 hours) followed py 7-10 days out-hospital oral ab. | ||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The summary include results from primary endpoint at hospital discharge. Further information from entire study period is available in the publication. | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/38218686 |
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