Timing of Primary Surgery for Cleft Palate (TOPS)

This trial is a randomised controlled trial with a parallel design taking place in centres across the UK, Scandinavia and Brazil.

650 infants with a diagnosis of isolated cleft palate who are considered medically fit for operation at 6 months, and who meet the inclusion criteria, will be included in the trial and randomised to receive either:

• Surgery at age 6 months, OR
• Surgery at age 12 months.

The main objective is to determine whether surgery for cleft palate, using a Sommerlad technique, at age 6 months, when compared to surgery using the same technique at age 12 months, improves velopharyngeal function at age 5 years. All infants will be followed up at age 12 months, 3 years and five years for the assessment of the primary outcomes( at age 5 years) and secondary outcomes.

Study Overview

• Status: Completed
• Conditions: Cleft Palate
• Intervention / Treatment: Procedure: primary surgery for cleft palate

Detailed Description

Infants will be followed up at age 12 months, 3 years and five years. At each visit the following will be assessed:

Age 12 months

• Speech development (canonical babbling)
• Audiological assessments
• Growth

Age 3 years

• Speech development
• Audiological assessments

Age 5 Years

• Speech development
• Audiological assessments
• Dentofacial development (Soft Tissue ANB and Maxillary arch constriction score using modified Huddart Bodenham scoring)

• Study Type: Interventional
• Enrollment (Actual): 558
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Bauru, Brazil
    • University of Sao Paulo
• Denmark
  • Aarhus, Denmark
    • Århus Speech and Hearing Institute
  • Copenhagen, Denmark
    • Copenhagen Cleft Palate Centre
• Norway
  • Bergen, Norway
    • Helse Bergen HF
  • Oslo, Norway
    • Oslo University Hospital
• Sweden
  • Gothenburg, Sweden
    • Göteborg University
  • Linköping, Sweden
    • University of Linköping
  • Malmö, Sweden
    • Malmö University Hospital
  • Stockholm, Sweden
    • Karolinska University Hospital
  • Umeå, Sweden
    • Umeå University
  • Uppsala, Sweden
    • Uppsala University
• United Kingdom
  • Belfast, United Kingdom
    • Belfast Health And Social Care Trust
  • Birmingham, United Kingdom
    • Birmingham Children's NHS Foundation Trust
  • Bristol, United Kingdom
    • North Bristol NHS Foundation Trust
  • Edinburgh, United Kingdom
    • Edinburgh Hospital for Sick Children
  • Glasgow, United Kingdom
    • NHS Greater Glasgow and Clyde
  • Leeds, United Kingdom
    • Leeds University Hospitals NHS foundation Trust
  • Liverpool, United Kingdom, L12 2AP
    • Alder Hey Children's NHS Foundation Trust
  • Manchester, United Kingdom, M13 9WL
    • Manchester University NHS Foundation Trust
  • Newcastle, United Kingdom
    • Newcastle University Hospitals NHs Foundation Trust
  • Oxford, United Kingdom
    • Oxford University Hospitals NHS Trust
  • Salisbury, United Kingdom
    • Salisbury District Hospital
  • Swansea, United Kingdom
    • Abertawe Bro Morgannwg University Health Board

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Infants with isolated cleft palate
• Medically fit for operation at 6 months, corrected for gestational age
• Written informed proxy consent
• One parent/carer a native language speaker in the country of residence

Exclusion Criteria:

• Consent not obtained
• b. Infants with syndromic cleft palate (except Van der Woude syndrome, which can be included if hearing is not affected) or severe developmental delay
• Congenital sensorineural hearing loss or middle ear anomalies;
• Variation in the anatomical presentation is such that the surgeon who will perform the procedure considers that one stage closure with the Sommerlad technique would be inappropriate;
• Submucous cleft palate (defined by the classical triad of signs, bifid, uvula, bony defect of the hard palate, muscular diastasis, as described by Jensen et al (1988).
• Where the language spoken at home is not the majority language in the country of residence.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 12 month surgery; Infants will receive primary surgery at age 12 months using Sommerlad technique	Procedure: primary surgery for cleft palate; Surgery completed using the Sommerlad technique
Experimental: 6 month surgery; Infants will receive primary surgery at age 6 months using Sommerlad technique.	Procedure: primary surgery for cleft palate; Surgery completed using the Sommerlad technique

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insufficient Velopharyngeal Function	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.	5 years of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Velopharyngeal Composite Score Summary (VPC Sum)	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
Insufficient Velopharyngeal Function	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.	3 & 5 years of age
Velopharyngeal Insufficiency Symptoms	The percentage of times that a target consonant uttered has a VPI symptom	3 years of age
Canonical Babbling Present	Presence of canonical babbling of syllables	1 year of age
Canonical Babbling Ratio	The proportion of times that a syllable produced is "canonical"	1 year of age
Canonical Babbling Consonant Inventory	The number of unique consonants produced	1 year of age
Articulation: Percent Consonant Correct (PCC)	The percentage of times that a target consonant is uttered correct	3 and 5 years of age
Articulation: Percent Correct Placement (PCP)	Percentage of times that a target consonant has the correct place of articulation	3 and 5 years of age
Articulation: Percent Correct Manner (PCM)	Percentage of times that a target consonant has the correct manner of articulation	3 and 5 years of age
Articulation: Non-oral Consonant Errors	Percentage of times that a target consonant is realised as a non-oral error	3 and 5 years of age
Articulation: Oral Consonant Errors	Percentage of times that a target consonant is realised as an oral error	3 and 5 years of age
Postoperative/Long Term Complications: Dehiscence	Assessment for presence (indicated as yes on a dichotomized scale of yes/no) of postoperative/long term complication of dehiscence reported as percentage.	Up to 30 days postoperatively
Postoperative/Long Term Complications: Infection	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	Up to 30 days postoperatively
Postoperative/Long Term Complications: Evidence of Fistula	Measured by assessment for presence (yes on a dichotomised scale of yes/no) for evidence of fistula, reported as percentage	Up to 5 years of age
Hearing Level: Abnormal Transient Otoacoustic Emission (TEOAE)	A dichotomous outcome of whether the child has abnormal TEOAE, reported percentage of participants that were abnormal.	1 year of age
Hearing Level: Abnormal Soundfield Audiometry	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.	1 year of age
Hearing Level: Abnormal Puretone Audiometry in at Least One Ear.	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.	3 and 5 years of age
Hearing Level: Abnormal Puretone Audiometry in Both Ears	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.	3 and 5 years of age
Hearing Level: Severity of Better Ear	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	3 and 5 years of age
Middle Ear Function: Flat Line Tympanogram in at Least One Ear	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.	1, 3 and 5 years of age
Middle Ear Function: Flat Line Tympanogram in Both Ears	Middle ear function is assessed by presence of flat line Tympanogram in both ears. Reported as percentage of participants with abnormal outcome.	1, 3 and 5 years of age
Dentofacial Development: Soft Tissue ANB	The angle between soft tissue nasion, A point, and B point on a profile photograph. The unit of measure is angular degrees	5 years of age
Dentofacial Development: Maxillary Arch Constriction Score	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.	5 years of age
Growth: Nude Weight	Growth: Nude weight measured in kg	1 year of age
Growth: Crown to Heel Length	Measured in centimetres and recorded to one decimal place.	1 year of age
Growth: Occiptofrontal Circumference	Measured in centimetres and recorded to one decimal place.	1 year of age

Collaborators and Investigators

• Sponsor: Kevin Munro
• Collaborators: Göteborg University; University of Copenhagen; National Institute of Dental and Craniofacial Research (NIDCR); University of Liverpool
• Investigators: Principal Investigator: Kevin J Munro, University of Manchester

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): March 26, 2021

Study Registration Dates

• First Submitted: October 9, 2009
• First Submitted That Met QC Criteria: October 9, 2009
• First Posted (Estimated): October 12, 2009

Study Record Updates

• Last Update Posted (Actual): September 2, 2026
• Last Update Submitted That Met QC Criteria: August 11, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: pediatric; surgery; cleft palate; speech; paediatric; velopharyngeal
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Mouth Diseases; Stomatognathic Diseases; Jaw Diseases; Jaw Abnormalities; Maxillofacial Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Stomatognathic System Abnormalities; Congenital Abnormalities; Mouth Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Behavior; Communication; Verbal Behavior; Cleft Palate; Speech; cyclopropapyrroloindole
• Other Study ID Numbers: 09-017-E; 1U01DE018837-01A1 (U.S. NIH Grant/Contract); Sponsor Reference: 57201 (Other Identifier: The University of Manchester (UK)); NIHR Portfolio Reference 30200 (Other Identifier: NIHR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data anonymised (participants and Speech and Language Therapists)
• IPD Sharing Time Frame: Immediately and up to 5 years after publication of the main paper
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal and ethical approval as appropriate
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP