Timing of Primary Surgery for Cleft Palate

NCT00993551 | Completed Results DMC

• 4 other identifiers: 09-017-E1U01DE018837-01A1Sponsor Reference: 57201NIHR Portfolio Reference 30200
• Study Type: interventional
• Target: 558
• Locations: 5 countries
• Sites: 23

Brief Summary

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.

Conditions

Cleft Palate

Keywords

cleft palate; paediatric; pediatric; surgery; speech; velopharyngeal

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (26)

• Velopharyngeal Composite Score Summary (VPC Sum)

  5 years of age

• Insufficient Velopharyngeal Function

  3 & 5 years of age

• Velopharyngeal Insufficiency Symptoms

  3 years of age

• Canonical Babbling Present

  1 year of age

• Canonical Babbling Ratio

  1 year of age

Study Arms (2)

12 month surgery

EXPERIMENTAL

Infants will receive primary surgery at age 12 months using Sommerlad technique

Procedure: primary surgery for cleft palate

6 month surgery

EXPERIMENTAL

Infants will receive primary surgery at age 6 months using Sommerlad technique.

Procedure: primary surgery for cleft palate

Interventions

primary surgery for cleft palate PROCEDURE

Surgery completed using the Sommerlad technique

12 month surgery; 6 month surgery

Eligibility Criteria

• Age: Up to 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kevin Munro: lead
• University of Liverpool: collaborator
• National Institute of Dental and Craniofacial Research (NIDCR): collaborator
• University of Copenhagen: collaborator
• Göteborg University: collaborator

Study Sites (23)

University of Sao Paulo

Bauru, Brazil

Location

Århus Speech and Hearing Institute

Aarhus, Denmark

Location

Copenhagen Cleft Palate Centre

Copenhagen, Denmark

Location

Helse Bergen HF

Bergen, Norway

Location

Oslo University Hospital

Oslo, Norway

Location

Göteborg University

Gothenburg, Sweden

Location

University of Linköping

Linköping, Sweden

Location

Malmö University Hospital

Malmö, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Umeå University

Umeå, Sweden

Location

Uppsala University

Uppsala, Sweden

Location

Belfast Health and Social Care Trust

Belfast, United Kingdom

Location

Birmingham Children's NHS Foundation Trust

Birmingham, United Kingdom

Location

North Bristol NHS Foundation Trust

Bristol, United Kingdom

Location

Edinburgh Hospital for Sick Children

Edinburgh, United Kingdom

Location

NHS Greater Glasgow and Clyde

Glasgow, United Kingdom

Location

Leeds University Hospitals NHS foundation Trust

Leeds, United Kingdom

Location

Alder Hey Children's NHS Foundation Trust

Liverpool, L12 2AP, United Kingdom

Location

Manchester University NHS Foundation Trust

Manchester, M13 9WL, United Kingdom

Location

Newcastle University Hospitals NHs Foundation Trust

Newcastle, United Kingdom

Location

Oxford University Hospitals NHS Trust

Oxford, United Kingdom

Location

Salisbury District Hospital

Salisbury, United Kingdom

Location

Abertawe Bro Morgannwg University Health Board

Swansea, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 39791255 DERIVED

• 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.

  PMID: 37646677 DERIVED

• 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.

  PMID: 35100923 DERIVED

• 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.

  PMID: 33397459 DERIVED

• 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.

  PMID: 31300507 DERIVED

MeSH Terms

Conditions

Cleft Palate; Speech

Interventions

cyclopropapyrroloindole

Condition Hierarchy (Ancestors)

Jaw Abnormalities; Jaw Diseases; Musculoskeletal Diseases; Maxillofacial Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Stomatognathic Diseases; Mouth Abnormalities; Mouth Diseases; Stomatognathic System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Verbal Behavior; Communication; Behavior

Results Point of Contact

• Title: Professor Carrol Gamble
• Organization: University of Liverpool

lctc@liverpool.ac.uk

0151 794 9759

Study Officials

• Kevin J Munro

  University of Manchester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Audiology

Study Record Dates

• First Submitted: October 9, 2009
• First Posted: October 12, 2009
• Study Start: July 1, 2010
• Primary Completion: August 1, 2020
• Study Completion: March 26, 2021
• Last Updated: September 2, 2026
• Results First Posted: September 2, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Immediately and up to 5 years after publication of the main paper
• Access Criteria: Researchers who provide a methodologically sound proposal and ethical approval as appropriate

Locations

BR (1); NO (2); SE (6); DK (2); GB (12)