Timing af primær kirurgi for ganespalte (TOPS)
11. august 2026 opdateret af: Kevin Munro
Dette forsøg er et randomiseret kontrolleret forsøg med et parallelt design, der finder sted i centre over hele Storbritannien, Skandinavien og Brasilien.
650 spædbørn med en diagnose af isoleret ganespalte, som anses for medicinsk egnet til operation efter 6 måneder, og som opfylder inklusionskriterierne, vil blive inkluderet i forsøget og randomiseret til at modtage enten:
- Operation i en alder af 6 måneder, ELLER
- Operation i en alder af 12 måneder.
Hovedformålet er at afgøre, om kirurgi for ganespalte, ved hjælp af en Sommerlad-teknik, i en alder af 6 måneder, sammenlignet med kirurgi ved brug af samme teknik i en alder af 12 måneder, forbedrer velopharyngeal funktion i en alder af 5 år. Alle spædbørn vil blive fulgt op i alderen 12 måneder, 3 år og fem år til vurdering af de primære resultater (i alderen 5 år) og sekundære resultater.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Spædbørn vil blive fulgt op i alderen 12 måneder, 3 år og fem år. Ved hvert besøg vil følgende blive vurderet:
Alder 12 måneder
- Taleudvikling (kanonisk pludren)
- Audiologiske vurderinger
- Vækst
Alder 3 år
- Taleudvikling
- Audiologiske vurderinger
Alder 5 år
- Taleudvikling
- Audiologiske vurderinger
- Dentofacial udvikling (Blødt væv ANB og Maxillary arch constriction score ved hjælp af modificeret Huddart Bodenham-scoring)
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
558
Fase
- Ikke anvendelig
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Bauru, Brasilien
- University of Sao Paulo
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Aarhus, Danmark
- Århus Speech and Hearing Institute
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Copenhagen, Danmark
- Copenhagen Cleft Palate Centre
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Belfast, Det Forenede Kongerige
- Belfast Health And Social Care Trust
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Birmingham, Det Forenede Kongerige
- Birmingham Children's NHS Foundation Trust
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Bristol, Det Forenede Kongerige
- North Bristol NHS Foundation Trust
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Edinburgh, Det Forenede Kongerige
- Edinburgh Hospital for Sick Children
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Glasgow, Det Forenede Kongerige
- NHS Greater Glasgow and Clyde
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Leeds, Det Forenede Kongerige
- Leeds University Hospitals NHS foundation Trust
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Liverpool, Det Forenede Kongerige, L12 2AP
- Alder Hey Children's NHS Foundation Trust
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Manchester, Det Forenede Kongerige, M13 9WL
- Manchester University NHS Foundation Trust
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Newcastle, Det Forenede Kongerige
- Newcastle University Hospitals NHs Foundation Trust
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Oxford, Det Forenede Kongerige
- Oxford University Hospitals NHS Trust
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Salisbury, Det Forenede Kongerige
- Salisbury District Hospital
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Swansea, Det Forenede Kongerige
- Abertawe Bro Morgannwg University Health Board
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Bergen, Norge
- Helse Bergen HF
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Oslo, Norge
- Oslo University Hospital
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Gothenburg, Sverige
- Göteborg University
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Linköping, Sverige
- University of Linköping
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Malmö, Sverige
- Malmö University Hospital
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Stockholm, Sverige
- Karolinska University Hospital
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Umeå, Sverige
- Umeå University
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Uppsala, Sverige
- Uppsala University
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
Ikke ældre end 6 måneder (Barn)
Tager imod sunde frivillige
Ingen
Beskrivelse
Inklusionskriterier:
- Spædbørn med isoleret ganespalte
- Medicinsk egnet til operation ved 6 måneder, korrigeret for gestationsalder
- Skriftlig informeret fuldmagtssamtykke
- En forælder/plejer har et modersmål i bopælslandet
Ekskluderingskriterier:
- Samtykke ikke opnået
- b. Spædbørn med syndromisk ganespalte (undtagen Van der Woude syndrom, som kan inkluderes, hvis hørelsen ikke er påvirket) eller alvorlig udviklingsforsinkelse
- Medfødt sensorineuralt høretab eller mellemøreanomalier;
- Variationen i den anatomiske præsentation er sådan, at den kirurg, der skal udføre proceduren, mener, at et trins lukning med Sommerlad-teknikken ville være uhensigtsmæssig;
- Submukøs ganespalte (defineret af den klassiske triade af tegn, bifid, drøvle, knogledefekt i den hårde ganespalte, muskulær diastase, som beskrevet af Jensen et al (1988).
- Hvor det sprog, der tales i hjemmet, ikke er majoritetssproget i bopælslandet.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: 12 måneders operation
Spædbørn vil blive primæropereret i en alder af 12 måneder ved hjælp af Sommerlad-teknik
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Operation afsluttet med Sommerlad-teknikken
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Eksperimentel: 6 måneders operation
Spædbørn vil blive primæropereret i en alder af 6 måneder ved hjælp af Sommerlad-teknik.
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Operation afsluttet med Sommerlad-teknikken
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Insufficient Velopharyngeal Function
Tidsramme: 5 years of age
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Measured by the Velopharyngeal Composite Score (VPC sum), which is a sum of scores, based on three components: hypernasality, non-oral errors, and VPI symptoms.
Each component is scored between 0 and 2. The sum of the three scores gives the VPC sum (0-6).
Scores ≥ 4 on this scale are considered insufficient (higher scores indicate a worse outcome).
This outcome is measured as a dichotomous variable (insufficient or not insufficient) with a cut-off threshold of ≥ 4 to indicate insufficient.
We report this as a percentage of participants that are assessed as having insufficient velopharyngeal function.
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5 years of age
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Velopharyngeal Composite Score Summary (VPC Sum)
Tidsramme: 5 years of age
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Measured by the Velopharyngeal Composite Score (VPC sum), which is a sum of scores, based on three components: hypernasality, non-oral errors, and VPI symptoms. Each component is scored between 0 and 2. The sum of the three scores gives the VPC sum (0-6). Higher scores indicate increased severity. |
5 years of age
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Insufficient Velopharyngeal Function
Tidsramme: 3 & 5 years of age
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Velopharyngeal function (VPC rate) measured on a 3 point scale; insufficient, marginal or sufficient.
Scale is dichotomised into insufficient or marginal/sufficient (with lower score indicating insufficient).
Reported as percentage of participants with insufficient function.
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3 & 5 years of age
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Velopharyngeal Insufficiency Symptoms
Tidsramme: 3 years of age
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The percentage of times that a target consonant uttered has a VPI symptom
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3 years of age
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Canonical Babbling Present
Tidsramme: 1 year of age
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Presence of canonical babbling of syllables
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1 year of age
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Canonical Babbling Ratio
Tidsramme: 1 year of age
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The proportion of times that a syllable produced is "canonical"
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1 year of age
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Canonical Babbling Consonant Inventory
Tidsramme: 1 year of age
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The number of unique consonants produced
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1 year of age
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Articulation: Percent Consonant Correct (PCC)
Tidsramme: 3 and 5 years of age
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The percentage of times that a target consonant is uttered correct
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3 and 5 years of age
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Articulation: Percent Correct Placement (PCP)
Tidsramme: 3 and 5 years of age
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Percentage of times that a target consonant has the correct place of articulation
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3 and 5 years of age
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Articulation: Percent Correct Manner (PCM)
Tidsramme: 3 and 5 years of age
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Percentage of times that a target consonant has the correct manner of articulation
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3 and 5 years of age
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Articulation: Non-oral Consonant Errors
Tidsramme: 3 and 5 years of age
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Percentage of times that a target consonant is realised as a non-oral error
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3 and 5 years of age
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Articulation: Oral Consonant Errors
Tidsramme: 3 and 5 years of age
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Percentage of times that a target consonant is realised as an oral error
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3 and 5 years of age
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Postoperative/Long Term Complications: Dehiscence
Tidsramme: Up to 30 days postoperatively
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Assessment for presence (indicated as yes on a dichotomized scale of yes/no) of postoperative/long term complication of dehiscence reported as percentage.
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Up to 30 days postoperatively
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Postoperative/Long Term Complications: Infection
Tidsramme: Up to 30 days postoperatively
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A dichotomous outcome of whether the child has a postoperative infection (indicated as yes on a dichotomized scale of yes/no) reported as a percentage
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Up to 30 days postoperatively
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Postoperative/Long Term Complications: Evidence of Fistula
Tidsramme: Up to 5 years of age
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Measured by assessment for presence (yes on a dichotomised scale of yes/no) for evidence of fistula, reported as percentage
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Up to 5 years of age
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Hearing Level: Abnormal Transient Otoacoustic Emission (TEOAE)
Tidsramme: 1 year of age
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A dichotomous outcome of whether the child has abnormal TEOAE, reported percentage of participants that were abnormal.
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1 year of age
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Hearing Level: Abnormal Soundfield Audiometry
Tidsramme: 1 year of age
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A dichotomous outcome of whether the child has abnormal sound field audiometry.
Abnormal sound field audiometry is indicated by a measurement of >30 dB HL for at least one of four frequencies tested: 500 Hz, 1000 Hz, 2000 Hz or 4000 Hz.
Reported as percentage of participants with abnormal outcome.
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1 year of age
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Hearing Level: Abnormal Puretone Audiometry in at Least One Ear.
Tidsramme: 3 and 5 years of age
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A dichotomous outcome of whether the child has abnormal pure tone audiometry.
If testing by pure tone audiometry is not possible, sound field audiometry can be used in its place.
Abnormal audiometry in at least one ear is indicated by a measurement of >20 dB HL using the pure tone method, >25 dB HL for sound field, for at least one of four frequencies tested: 500 Hz, 1000 Hz, 2000 Hz or 4000 Hz.Reported as percentage of participants with abnormal outcome.
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3 and 5 years of age
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Hearing Level: Abnormal Puretone Audiometry in Both Ears
Tidsramme: 3 and 5 years of age
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A dichotomous outcome defined in the same way as Abnormal Puretone Audiometry in at least one ear.
For participants who have both ears tested and both tested ears indicate abnormal audiometry.
Reported as percentage of participants with abnormal outcome.
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3 and 5 years of age
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Hearing Level: Severity of Better Ear
Tidsramme: 3 and 5 years of age
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Severity of hearing loss is measured in better ear is categorised as normal, mild, moderate, severe or profound.
Reported as percentage of participants with hearing outcome below normal
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3 and 5 years of age
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Middle Ear Function: Flat Line Tympanogram in at Least One Ear
Tidsramme: 1, 3 and 5 years of age
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Middle ear function is assessed by presence of flat line Tympanogram in at least one ear.
Reported as percentage of particpants with abnormal finding consistent with middle ear effusion.
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1, 3 and 5 years of age
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Middle Ear Function: Flat Line Tympanogram in Both Ears
Tidsramme: 1, 3 and 5 years of age
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Middle ear function is assessed by presence of flat line Tympanogram in both ears.
Reported as percentage of participants with abnormal outcome.
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1, 3 and 5 years of age
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Dentofacial Development: Soft Tissue ANB
Tidsramme: 5 years of age
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The angle between soft tissue nasion, A point, and B point on a profile photograph.
The unit of measure is angular degrees
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5 years of age
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Dentofacial Development: Maxillary Arch Constriction Score
Tidsramme: 5 years of age
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Maxillary arch constriction score: a bounded continuous outcome, measured using the Huddart/Bodenham scoring system, on a maxilliary and mandibular arches impression.
A score can range from -24 to 8. A positive score is good, with negative scores indicating maxillary constriction.
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5 years of age
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Growth: Nude Weight
Tidsramme: 1 year of age
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Growth: Nude weight measured in kg
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1 year of age
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Growth: Crown to Heel Length
Tidsramme: 1 year of age
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Measured in centimetres and recorded to one decimal place.
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1 year of age
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Growth: Occiptofrontal Circumference
Tidsramme: 1 year of age
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Measured in centimetres and recorded to one decimal place.
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1 year of age
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Kevin J Munro, University of Manchester
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- Willadsen E, Cooper R, Conroy E, Gamble C, Albery L, Andersen H, Appelqvist M, Bodling P, Bowden M, Brunnegard K, Enfalt J, van Eeden S, Goncalves C, Fukushiro A, Jorgensen L, Lemvik J, Leturgie L, Liljerehn E, Lodge N, McMahon S, Miguel H, Patrick K, Phippen G, Piazentin-Penna S, Southby L, Taleman AS, Tangstad J, Yamashita R, Shaw W, Munro K, Walsh T, Persson C. Inter-rater reliability in classification of canonical babbling status based on canonical babbling ratio in infants with isolated cleft palate randomised to Timing of Primary Surgery for Cleft Palate (TOPS). Clin Linguist Phon. 2023 Jan 2;37(1):77-98. doi: 10.1080/02699206.2021.2012259. Epub 2022 Jan 31.
- Conroy EJ, Cooper R, Shaw W, Persson C, Willadsen E, Munro KJ, Williamson PR, Semb G, Walsh T, Gamble C; TOPS trial management group. A randomised controlled trial comparing palate surgery at 6 months versus 12 months of age (the TOPS trial): a statistical analysis plan. Trials. 2021 Jan 4;22(1):5. doi: 10.1186/s13063-020-04886-y.
- Shaw W, Semb G, Lohmander A, Persson C, Willadsen E, Clayton-Smith J, Trindade IK, Munro KJ, Gamble C, Harman N, Conroy EJ, Weichart D, Williamson P. Timing Of Primary Surgery for cleft palate (TOPS): protocol for a randomised trial of palate surgery at 6 months versus 12 months of age. BMJ Open. 2019 Jul 11;9(7):e029780. doi: 10.1136/bmjopen-2019-029780.
- Conroy EJ, Blazeby JM, Burnside G, Cook JA, Gamble C. Investigating the presence of surgical learning in the Timing of Primary Surgery for cleft palate randomised trial. Clin Trials. 2025 Apr;22(2):200-208. doi: 10.1177/17407745241302488. Epub 2025 Jan 10.
- Gamble C, Persson C, Willadsen E, Albery L, Soegaard Andersen H, Zattoni Antoneli M, Appelqvist M, Aukner R, Bodling P, Bowden M, Brunnegard K, Cairns G, Calladine S, Campbell L, Clayton-Smith J, Cooper R, Conroy E, El-Angbawi A, Kildegaard Emborg B, Enfalt Wikman J, Fitzpatrick B, Fukushiro AP, Guedes de Azevedo Bento Goncalves C, Havstam C, Hvistendahl AK, Jorgensen LD, Klinto K, Berntsen Kvinnsland M, Larham C, Lemvik J, Leturgie L, Liljerehn E, Lodge N, Lohmander A, McMahon S, Mehendale F, Miguel HC, Moe M, Nielsen JB, Nyberg J, Pedersen NH, Phippen G, Alvarez Piazentin-Penna SH, Patrick K, Pliskin L, Rigby L, Semb G, Southby L, Sporre M, Bjorkman Taleman AS, Tangstad J, Trindade IEK, Underwood I, van Eeden S, Westberg LR, Williamson PR, Paciello Yamashita R, Munro K, Walsh T, Shaw W; TOPS Study Group. Timing of Primary Surgery for Cleft Palate. N Engl J Med. 2023 Aug 31;389(9):795-807. doi: 10.1056/NEJMoa2215162.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. juli 2010
Primær færdiggørelse (Faktiske)
1. august 2020
Studieafslutning (Faktiske)
26. marts 2021
Datoer for studieregistrering
Først indsendt
9. oktober 2009
Først indsendt, der opfyldte QC-kriterier
9. oktober 2009
Først opslået (Anslået)
12. oktober 2009
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
2. september 2026
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
11. august 2026
Sidst verificeret
1. august 2026
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Muskuloskeletale sygdomme
- Mundsygdomme
- Stomatognatiske sygdomme
- Kæbesygdomme
- Abnormiteter i kæben
- Maxillofacial abnormiteter
- Kraniofaciale abnormiteter
- Muskuloskeletale abnormiteter
- Stomatognatiske systemabnormiteter
- Medfødte abnormiteter
- Abnormiteter i munden
- Medfødte, arvelige og neonatale sygdomme og abnormiteter
- Opførsel
- Meddelelse
- Verbal opførsel
- Ganespalte
- Tale
- cyclopropapyrroloindole
Andre undersøgelses-id-numre
- 09-017-E
- 1U01DE018837-01A1 (U.S. NIH-bevilling/kontrakt)
- Sponsor Reference: 57201 (Anden identifikator: The University of Manchester (UK))
- NIHR Portfolio Reference 30200 (Anden identifikator: NIHR)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
JA
IPD-planbeskrivelse
Data anonymised (participants and Speech and Language Therapists)
IPD-delingstidsramme
Immediately and up to 5 years after publication of the main paper
IPD-delingsadgangskriterier
Researchers who provide a methodologically sound proposal and ethical approval as appropriate
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
- SAP
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .