Initial non-operative management of uncomplicated appendicitis in children: a protocol for a multicentre randomised controlled trial (APAC trial)

APAC collaborative study group; AUTHOR GROUP

doi:https://doi.org/10.1136/bmjopen-2017-018145

Initial non-operative management of uncomplicated appendicitis in children: a protocol for a multicentre randomised controlled trial (APAC trial)

APAC collaborative study group, AUTHOR GROUP

Research output: Contribution to journal › Article › Academic › peer-review

17 Citations (Scopus)

Abstract

INTRODUCTION: Based on epidemiological, immunological and pathology data, the idea that appendicitis is not necessarily a progressive disease is gaining ground. Two types are distinguished: simple and complicated appendicitis. Non-operative treatment (NOT) of children with simple appendicitis has been investigated in several small studies. So far, it is deemed safe. However, its effectiveness and effect on quality of life (QoL) have yet to be established in an adequately powered randomised trial. In this article, we provide the study protocol for the APAC (Antibiotics versus Primary Appendectomy in Children) trial.

METHODS AND ANALYSIS: This multicentre, non-inferiority, randomised controlled trial randomises children aged 7-17 years with imaging-confirmed simple appendicitis between appendectomy and NOT. Patients are recruited in 15 hospitals. The intended sample size, based on the primary outcome, rate of complications and a non-inferiority margin of 5%, is 334 patients.NOT consists of intravenous antibiotics for 48-72 hours, daily blood tests and ultrasound follow-up. If the patient meets the predefined discharge criteria, antibiotic treatment is continued orally at home. Primary outcome is the rate of complications at 1-year follow-up. An independent adjudication committee will assess all complications and their relation to the allocated treatment. Secondary outcomes include, but are not limited to, delayed appendectomies, QoL, pain and (in)direct costs.The primary outcome will be analysed both according to the intention-to-treat principle and the per-protocol principle, and is presented with a one-sided 97.5% CI. We will use multiple logistic and linear regression for binary and continuous outcomes, respectively, to adjust for stratification factors.

ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Ethics Review Committee of the Academic Medical Center, Amsterdam. Data monitoring is performed by an independent institute and a Data Safety Monitoring Board has been assigned. Results will be presented in peer-reviewed academic journals and at (international) conferences.

TRIAL REGISTRATION NUMBER: NCT02848820; NTR5977; Pre-results.

Original language	English
Pages (from-to)	e018145
Journal	BMJ Open
Volume	7
Issue number	11
DOIs	https://doi.org/10.1136/bmjopen-2017-018145
Publication status	Published - 15 Nov 2017

Keywords

Journal Article

Access to Document

https://doi.org/10.1136/bmjopen-2017-018145

Cite this

@article{3d0d2340745b4a2ba45087eeeec2e000,

title = "Initial non-operative management of uncomplicated appendicitis in children: a protocol for a multicentre randomised controlled trial (APAC trial)",

abstract = "INTRODUCTION: Based on epidemiological, immunological and pathology data, the idea that appendicitis is not necessarily a progressive disease is gaining ground. Two types are distinguished: simple and complicated appendicitis. Non-operative treatment (NOT) of children with simple appendicitis has been investigated in several small studies. So far, it is deemed safe. However, its effectiveness and effect on quality of life (QoL) have yet to be established in an adequately powered randomised trial. In this article, we provide the study protocol for the APAC (Antibiotics versus Primary Appendectomy in Children) trial.METHODS AND ANALYSIS: This multicentre, non-inferiority, randomised controlled trial randomises children aged 7-17 years with imaging-confirmed simple appendicitis between appendectomy and NOT. Patients are recruited in 15 hospitals. The intended sample size, based on the primary outcome, rate of complications and a non-inferiority margin of 5%, is 334 patients.NOT consists of intravenous antibiotics for 48-72 hours, daily blood tests and ultrasound follow-up. If the patient meets the predefined discharge criteria, antibiotic treatment is continued orally at home. Primary outcome is the rate of complications at 1-year follow-up. An independent adjudication committee will assess all complications and their relation to the allocated treatment. Secondary outcomes include, but are not limited to, delayed appendectomies, QoL, pain and (in)direct costs.The primary outcome will be analysed both according to the intention-to-treat principle and the per-protocol principle, and is presented with a one-sided 97.5% CI. We will use multiple logistic and linear regression for binary and continuous outcomes, respectively, to adjust for stratification factors.ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Ethics Review Committee of the Academic Medical Center, Amsterdam. Data monitoring is performed by an independent institute and a Data Safety Monitoring Board has been assigned. Results will be presented in peer-reviewed academic journals and at (international) conferences.TRIAL REGISTRATION NUMBER: NCT02848820; NTR5977; Pre-results.",

keywords = "Journal Article",

author = "{APAC collaborative study group} and Max Knaapen and {van der Lee}, {Johanna H} and Roel Bakx and The, {Sarah-May L} and {van Heurn}, {Ernst W E} and Heij, {Hugo A} and Gorter, {Ramon R} and {AUTHOR GROUP} and H. Rippen and Bet, {P. M.} and G. Kazemier and Kneepkens, {C. M. F.} and R. Wijnen and M. Offringa and N. Ahmadi and Bonjer, {H. J.} and {van Rijn}, {R. R.} and Benninga, {M. A.} and Bemelman, {W. A.} and Hilarius, {D. L.} and {van Veen}, {S. A. J. M.} and Go, {P. M. N. Y. H.} and Cense, {H. A.} and {de Vries}, A. and J. Straatman and {in {\textquoteright}t Hof}, {K. H.} and {van Beek}, {E. J. A. H.} and Bender, {M. H. M.} and {van den Hill}, {L. C. L.} and Bolhuis, {H. W.} and K. Treskes and Bijlsma, {T. S.} and N. Geubbels and {de Blaauw}, I. and Botden, {S. M. B. I.} and Leijdekkers, {V. J.} and Boonstra, {M. C.} and Rongen, {L. H.} and Boerma, {E. J. G.} and Luyer, {M. D. P.} and G. Vugts and T. Copper and Garssen, {F. P.} and C. Hulsker and Visschers, {R. G. J.}",

year = "2017",

month = nov,

day = "15",

doi = "https://doi.org/10.1136/bmjopen-2017-018145",

language = "English",

volume = "7",

pages = "e018145",

journal = "BMJ Open",

issn = "2044-6055",

publisher = "BMJ Publishing Group",

number = "11",

}

TY - JOUR

T1 - Initial non-operative management of uncomplicated appendicitis in children

T2 - a protocol for a multicentre randomised controlled trial (APAC trial)

AU - APAC collaborative study group

AU - Knaapen, Max

AU - van der Lee, Johanna H

AU - Bakx, Roel

AU - The, Sarah-May L

AU - van Heurn, Ernst W E

AU - Heij, Hugo A

AU - Gorter, Ramon R

AU - AUTHOR GROUP

AU - Rippen, H.

AU - Bet, P. M.

AU - Kazemier, G.

AU - Kneepkens, C. M. F.

AU - Wijnen, R.

AU - Offringa, M.

AU - Ahmadi, N.

AU - Bonjer, H. J.

AU - van Rijn, R. R.

AU - Benninga, M. A.

AU - Bemelman, W. A.

AU - Hilarius, D. L.

AU - van Veen, S. A. J. M.

AU - Go, P. M. N. Y. H.

AU - Cense, H. A.

AU - de Vries, A.

AU - Straatman, J.

AU - in ’t Hof, K. H.

AU - van Beek, E. J. A. H.

AU - Bender, M. H. M.

AU - van den Hill, L. C. L.

AU - Bolhuis, H. W.

AU - Treskes, K.

AU - Bijlsma, T. S.

AU - Geubbels, N.

AU - de Blaauw, I.

AU - Botden, S. M. B. I.

AU - Leijdekkers, V. J.

AU - Boonstra, M. C.

AU - Rongen, L. H.

AU - Boerma, E. J. G.

AU - Luyer, M. D. P.

AU - Vugts, G.

AU - Copper, T.

AU - Garssen, F. P.

AU - Hulsker, C.

AU - Visschers, R. G. J.

PY - 2017/11/15

Y1 - 2017/11/15

N2 - INTRODUCTION: Based on epidemiological, immunological and pathology data, the idea that appendicitis is not necessarily a progressive disease is gaining ground. Two types are distinguished: simple and complicated appendicitis. Non-operative treatment (NOT) of children with simple appendicitis has been investigated in several small studies. So far, it is deemed safe. However, its effectiveness and effect on quality of life (QoL) have yet to be established in an adequately powered randomised trial. In this article, we provide the study protocol for the APAC (Antibiotics versus Primary Appendectomy in Children) trial.METHODS AND ANALYSIS: This multicentre, non-inferiority, randomised controlled trial randomises children aged 7-17 years with imaging-confirmed simple appendicitis between appendectomy and NOT. Patients are recruited in 15 hospitals. The intended sample size, based on the primary outcome, rate of complications and a non-inferiority margin of 5%, is 334 patients.NOT consists of intravenous antibiotics for 48-72 hours, daily blood tests and ultrasound follow-up. If the patient meets the predefined discharge criteria, antibiotic treatment is continued orally at home. Primary outcome is the rate of complications at 1-year follow-up. An independent adjudication committee will assess all complications and their relation to the allocated treatment. Secondary outcomes include, but are not limited to, delayed appendectomies, QoL, pain and (in)direct costs.The primary outcome will be analysed both according to the intention-to-treat principle and the per-protocol principle, and is presented with a one-sided 97.5% CI. We will use multiple logistic and linear regression for binary and continuous outcomes, respectively, to adjust for stratification factors.ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Ethics Review Committee of the Academic Medical Center, Amsterdam. Data monitoring is performed by an independent institute and a Data Safety Monitoring Board has been assigned. Results will be presented in peer-reviewed academic journals and at (international) conferences.TRIAL REGISTRATION NUMBER: NCT02848820; NTR5977; Pre-results.

AB - INTRODUCTION: Based on epidemiological, immunological and pathology data, the idea that appendicitis is not necessarily a progressive disease is gaining ground. Two types are distinguished: simple and complicated appendicitis. Non-operative treatment (NOT) of children with simple appendicitis has been investigated in several small studies. So far, it is deemed safe. However, its effectiveness and effect on quality of life (QoL) have yet to be established in an adequately powered randomised trial. In this article, we provide the study protocol for the APAC (Antibiotics versus Primary Appendectomy in Children) trial.METHODS AND ANALYSIS: This multicentre, non-inferiority, randomised controlled trial randomises children aged 7-17 years with imaging-confirmed simple appendicitis between appendectomy and NOT. Patients are recruited in 15 hospitals. The intended sample size, based on the primary outcome, rate of complications and a non-inferiority margin of 5%, is 334 patients.NOT consists of intravenous antibiotics for 48-72 hours, daily blood tests and ultrasound follow-up. If the patient meets the predefined discharge criteria, antibiotic treatment is continued orally at home. Primary outcome is the rate of complications at 1-year follow-up. An independent adjudication committee will assess all complications and their relation to the allocated treatment. Secondary outcomes include, but are not limited to, delayed appendectomies, QoL, pain and (in)direct costs.The primary outcome will be analysed both according to the intention-to-treat principle and the per-protocol principle, and is presented with a one-sided 97.5% CI. We will use multiple logistic and linear regression for binary and continuous outcomes, respectively, to adjust for stratification factors.ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Ethics Review Committee of the Academic Medical Center, Amsterdam. Data monitoring is performed by an independent institute and a Data Safety Monitoring Board has been assigned. Results will be presented in peer-reviewed academic journals and at (international) conferences.TRIAL REGISTRATION NUMBER: NCT02848820; NTR5977; Pre-results.

KW - Journal Article

U2 - https://doi.org/10.1136/bmjopen-2017-018145

DO - https://doi.org/10.1136/bmjopen-2017-018145

M3 - Article

C2 - 29146647

SN - 2044-6055

VL - 7

SP - e018145

JO - BMJ Open

JF - BMJ Open

IS - 11

ER -