The main objective is to identify the optimal management for patients with an asymptomatic CPAM, based on functional outcome measures. Furthermore, the primary objective is to stratify asymptomatic CPAM patients into a low and high risk group for…
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Source
Brief title
Condition
- Respiratory disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome is the difference in maximal endurance using the BRUCE
treadmill test at five years of age between the surgical and conservative
group, measured in minutes and SDS.
Secondary outcome
o Pulmonary morbidity during follow-up (occurrence of infections, cough,
dyspnoea, respiratory insufficiency and other pulmonary symptoms).
o Frequency of surgical intervention due to pulmonary morbidity during
follow-up period
o CPAM characteristics on prenatal ultrasound images, reported according to
structured report, see Appendix D (35)
o CPAM characteristics on CT-scan at 3-9 months of age, reported according to
structured report form Appendix C (34)
o CPAM development / post-surgical appearance on repeated CT imaging, reported
according to structured report form (34)
o Parental anxiety, pre-operative and at all follow-up visits by means of the
Visual Analogue Scale for Anxiety (VAS-A) (38, 39)
o Quality of life analysis by means of the Infant Toddler Quality of Life
Questionnaire (ITQOL) (40)
o Pathological characteristics of resected material (macroscopic, microscopic,
immunohistochemistry, molecular diagnostics) as assessed by local
pathologist of participating centre according to Appendix B (23)
o Abnormal anthropometric measurements during follow-up, measured with help of
local SD-score computation
o Analysis of the cost-effectiveness of both management strategies and
comparison between them, see chapter 10-c
Background summary
Congenital Pulmonary Airway Malformation (CPAM), formerly known as Congenital
Cystic Adenomatoid Malformation (CCAM), is the most common congenital lung
abnormality (CLA), comprising approximately 30% of all CLA. A CPAM is a
congenital cystic lung lesion with an abnormal connection to the
tracheobronchial tree and normal pulmonary vascularization. Advances in
prenatal ultrasound have led to increased incidence figures, momentarily
estimating the incidence to be approximately 4 in 10,000 births. Despite the
increasing incidence, much is still unknown about the developmental causes,
best treatment options, and natural course of CPAM. When CPAM patients present
with symptoms, surgical resection is usually recommended. However, the majority
of CPAM patients are asymptomatic at birth and remain so during childhood. In
this case, a conservative wait-and-see management is propagated by some for
this originally benign, possibly regressive disease while others believe in an
operative approach. Arguments for early surgical resection include the risk of
symptom development, possibly indicating emergency surgery leading to an
increased risk of complications. Other arguments include the possible malignant
degeneration of these lesions, parental anxiety, and hypothetical compensatory
lung growth following early resection. Arguments in favour of expectant
management include the risk of postoperative complications, the fact that the
majority of patients will remain asymptomatic, and the evidence in literature
that surgical resection does not rule out the development of malignancy in the
lesion region. All abovementioned arguments are based on retrospective studies,
expert opinion or empiricism, but hard evidence is lacking. We hypothesize that
asymptomatic patients can be managed expectantly but must be structurally
monitored. As most patients remain asymptomatic, and to date no postnatal
predictors have been identified for the quality of life and daily activities in
this patient group, focus on functional outcome measures such as pulmonary
morbidity and endurance of physical activity is desirable.
Study objective
The main objective is to identify the optimal management for patients with an
asymptomatic CPAM, based on functional outcome measures. Furthermore, the
primary objective is to stratify asymptomatic CPAM patients into a low and high
risk group for developing symptoms, infection and malignant degeneration and to
hereby introduce a personalised medicine approach towards management.
Secondary objectives include the detection of predictive prenatal and postnatal
features and the assessment during follow up of: physical growth, psychomotor
development and pulmonary morbidity, parental anxiety, quality of life, and the
effectiveness of quantitative imaging in predicting outcome.
Study design
Randomised, controlled, multicentre superiority trial. Randomisation will take
place as centre specific block randomisation with 1:1 allocation.
One hundred and sixty-six patients will be recruited within a multinational
European consortium (the CONNECT consortium).
Intervention
Children assigned to the intervention group will undergo surgical resection of
the CPAM between 6 and 9 months of age. Children assigned to the control group
will be monitored conservatively. The follow-up scheme will be uniform for both
treatment groups and last for 5 years.
Study burden and risks
The risk and burden of pulmonary resection in asymptomatic CPAM patients is
low. It is currently the standard care for this patient group in the majority
of centres globally (67-77%). On the other hand, a conservative follow-up is
considered a safe and viable alternative (standard of care in 23-33% of
centres), as only a fraction (3-9%) of initially asymptomatic CPAM patients
goes on to develop symptoms during the first years of life. The burden of the
follow-up scheme in this trial is considered low and is also standard of care
in participating centres. The added knowledge gained by analysing the
longitudinal information attained by the second CT-scan & the questionnaires
outweighs the burden of this procedure and the radiation exposure.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
- Lesion detected during routine prenatal ultrasound screening
- Delivery at term: gestational age >=37 weeks
- Birthweight > -2SD or >P10
- Asymptomatic at birth defined as no prolonged respiratory distress or oxygen
support (< 24 hours)
- Asymptomatic up to the moment of inclusion
- Confirmation of CPAM on postnatal chest CT-scan at 3-9 months of age,
according to structured report form
- Unilateral lesion occupying no more than one lung lobe as assessed on chest
CT-scan at 3-9 months of age
Exclusion criteria
- Bilateral lesion
- Development of symptoms before randomization, considered by treating
physician as caused by CPAM with reasonable certainty
- Complicated pregnancy defined as (pre-)eclampsia, pregnancy diabetes in
mother, foetal hydrops or severe polyhydramnios on prenatal ultrasound
- Syndrome associated anomalies on genetic analysis confirmed by genetic expert
- Major associated malformations. Anomalies include cardiac malformations
requiring surgical correction or follow-up by a paediatric cardiologist,
congenital malformations requiring major surgical intervention, and anomalies
that affect normal lung growth and development.
- Suspicion of malignancy on chest CT scan evaluation at the age of 3-9 months
- Participation in another randomised controlled trial
Design
Recruitment
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 |
|---|---|
| CCMO | NL81003.078.22 |