## Protocol Section
### Identification Module
**NCT ID:** NCT06069479

**Acronym:** Treat Trigono

**Brief Title:** Comparing Conservative to Surgical Treatment of Trigonocephaly Craniofacial Surgery in Children With Trigonocephaly: an Observational Cohort Study on Clinical Outcomes, Psychosocial Wellbeing, and Costs

**Official Title:** Comparing Effectiveness of a Conservative Policy to Craniofacial Surgery in Children With Trigonocephaly: an Observational Cohort Study on Clinical Outcomes, Psychosocial Wellbeing, and Costs

#### Organization Study ID Info
**ID:** PaNaMaID 9517
#### Organization
**Class:** OTHER
**Full Name:** Erasmus Medical Center
### Status Module
#### Completion Date
**Date:** 2031-08-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-10-05

**Type:** ACTUAL

**Last Update Submit Date:** 2023-10-02

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2031-02-28

**Type:** ESTIMATED

#### Start Date
**Date:** 2022-09-01

**Type:** ACTUAL

**Status Verified Date:** 2023-10

#### Study First Post Date
**Date:** 2023-10-05
**Type:** ACTUAL
**Study First Submit Date:** 2023-10-02
**Study First Submit QC Date:** 2023-10-02
### Sponsor Collaborators Module

#### Collaborators

**Class:** UNKNOWN

**Name:** LAPOSA

**Class:** UNKNOWN

**Name:** IJsselland ziekenhuis

**Class:** OTHER

**Name:** Sint Franciscus Gasthuis

#### Lead Sponsor

**Class:** OTHER

**Name:** Erasmus Medical Center

#### Responsible Party

**Investigator Affiliation:** Erasmus Medical Center

**Investigator Full Name:** Irene Mathijssen

**Investigator Title:** prof.dr. MBA-H

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** RESEARCH QUESTION Is the effectiveness of conservative policy comparable to that of surgery in children with trigonocephaly, with regard to clinical outcomes and psychosocial functioning, stress for parents, and costs? DESIGN Observational cohort study in children, aged 0 to 8 years old, with trigonocephaly, excluding metopic ridging (physiologic early closure of metopic suture), treated conservatively or surgically.

OUTCOME MEASURES Primary: Head growth decline, indicating raised intracranial pressure Secondary: fundoscopy, cognition, behavior, refraction and vision, forehead shape, quality of life, posttraumatic stress, decisional conflict, costs.

**Detailed Description:** HYPOTHESIS Conservative treatment is non-inferior to surgery with regard to clinical outcomes, causes less burden of disease, and is cost-effective.

STUDY DESIGN Observational cohort study STUDY POPULATION Children, aged 0 to 8 years old, with trigonocephaly, excluding metopic ridging (physiologic early closure of metopic suture) INTERVENTION Conservative policy USUAL CARE/COMPARISON Craniofacial surgery OUTCOME MEASURES Primary: Head growth decline (head circumference in SD), indicating raised intracranial pressure Secondary: fundoscopy, cognition, behavior, refraction and vision, forehead shape, quality of life, posttraumatic stress, decisional conflict, costs. Repeated measures at 0, 2, 4, 6, 8 years of age SAMPLE SIZE/DATA ANALYSIS Eligible patients \<= 3 years of age are included since Sept 2022 Sample size 440 patients \<1 year of age: 195 surgery and 245 conservative

Non-inferiority with regard to head growth from 0-4 years (annual measurement) is determined using a linear mixed model adjusted for confounders:

severity of phenotype, sex, syndrome and parental factors (e.g., education). COST-EFFECTIVINESS ANALYSIS/BIA An economic evaluation is performed with the incorporation of medical costs and costs due to loss of productivity for the parents. A detailed costs-study is done for medical specialist care, surgical costs, hospitalization and other costs directly associated with the interventions. Cost prizes of surgery will be determined by the bottom-up micro-costing method. Cost-utility will be measured with QALY (based on EQ-5D utility score) gained, with confidence ellipses and acceptability curves. The impact of conservative policy versus surgery will be investigated on assurance perspective and central level. From the viewpoint of the (health care) government, a societal perspective and perspective of the "budgettair kader zorg" will be highlighted. We will provide a valid framework with budget consequences by a range of predictions. Sensitivity analysis is done.

TIME SCHEDULE Inclusion between Sept 2022 and Sept 2030. Analysis and reporting for each outcome parameter related to age is distributed from January 2025 to September 2031. New recommendation for treatment of trigonocephaly in guideline ready in 2031.

### Conditions Module

**Conditions:**

- Metopic Synostosis

### Design Module

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 440

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Children with trigonocephaly that are treated conservatively.

**Label:** Conservative group

#### Arm Group 2

**Description:** Children with trigonocephaly that are treated surgically.

**Intervention Names:**

- Procedure: craniofacial surgery

**Label:** Surgical group

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Surgical group

**Description:** Surgical treatment, either stripcraniectomy or fronto-orbital advancement

**Name:** craniofacial surgery

**Type:** PROCEDURE

### Outcomes Module

#### Primary Outcomes

**Description:** Annual measurement of head circumference in SD for gender and age. Decline in head growth may indicate raised intracranial pressure

**Measure:** Head growth

**Time Frame:** from 0 to 8 years old

#### Secondary Outcomes

**Description:** Annual screening for presence of papilledema as sign of raised intracranial pressure

**Measure:** fundoscopy

**Time Frame:** from 1 to 4 years old

**Description:** Validated tests for cognition and behavior of the child

**Measure:** Cognition and behavior

**Time Frame:** at 0, 2, 4 and 8 years old

**Description:** tests taken by orthoptist

**Measure:** refraction and vision

**Time Frame:** at 1, 4 and 8 years old

**Description:** 3D photos (objective) and VAS score by parents (subjective) to grade the forehead shape

**Measure:** forehead shape

**Time Frame:** at 0, 2, 4, 6 and 8 years old

**Description:** Validated tests to measure quality of life of the child and parents and presence of PTS in parents

**Measure:** Quality of life and post-traumatic stress

**Time Frame:** at 0, 2, 4, 6 and 8 years old

**Description:** questionnaire to determine whether or not parents are still content with their decision on type of treatment

**Measure:** Decisional conflict

**Time Frame:** at 8 years old

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* diagnosis of trigonocephaly

Exclusion Criteria:

* metopic ridge (physiologic early closure of metopic suture)

**Maximum Age:** 8 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- CHILD

**Study Population:** Children with mild, moderate or severe trigonocephaly, between 0 and 8 years of age, excluding metopic ridge (i.e. physiologic early closure of metopic suture).

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** i.mathijssen@erasmusmc.nl

**Name:** Irene MJ Mathijssen, MD, PhD, MBA-H

**Phone:** +31655758441

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Rotterdam

**Contacts:**

***Contact 1:***

- **Email:** i.mathijssen@erasmusmc.nl

- **Name:** Irene MJ Mathijssen, MD, PhD, MBA-H

- **Phone:** +31655758441

- **Role:** CONTACT

**Country:** Netherlands

**Facility:** Erasmus MC

**Status:** RECRUITING

**Zip:** 3012LE

#### Overall Officials

**Official 1:**

**Affiliation:** Erasmus Medical Center

**Name:** Irene MJ Mathijssen, MD, PhD, MBA-H

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Cornelissen MJ, Loudon SE, van Doorn FEC, Muller RPM, van Veelen MC, Mathijssen IMJ. Very Low Prevalence of Intracranial Hypertension in Trigonocephaly. Plast Reconstr Surg. 2017 Jan;139(1):97e-104e. doi: 10.1097/PRS.0000000000002866.

**PMID:** 28027242

**Citation:** de Planque CA, Petr J, Gaillard L, Mutsaerts HJMM, van Veelen MC, Versnel SL, Dremmen MHG, Mathijssen IMJ. Cerebral Blood Flow of the Frontal Lobe in Untreated Children with Trigonocephaly versus Healthy Controls: An Arterial Spin Labeling Study. Plast Reconstr Surg. 2022 Apr 1;149(4):931-937. doi: 10.1097/PRS.0000000000008931.

**PMID:** 35171857

**Citation:** Mathijssen IMJ; Working Group Guideline Craniosynostosis. Updated Guideline on Treatment and Management of Craniosynostosis. J Craniofac Surg. 2021 Jan-Feb 01;32(1):371-450. doi: 10.1097/SCS.0000000000007035. No abstract available.

**PMID:** 33156164

**Citation:** Abdel-Alim T, Iping R, Wolvius EB, Mathijssen IMJ, Dirven CMF, Niessen WJ, van Veelen MC, Roshchupkin GV. Three-Dimensional Stereophotogrammetry in the Evaluation of Craniosynostosis: Current and Potential Use Cases. J Craniofac Surg. 2021 May 1;32(3):956-963. doi: 10.1097/SCS.0000000000007379.

**PMID:** 33405445

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000004413

- Term: Dysostoses

- ID: D000001848

- Term: Bone Diseases, Developmental

- ID: D000001847

- Term: Bone Diseases

- ID: D000009140

- Term: Musculoskeletal Diseases

- ID: D000009139

- Term: Musculoskeletal Abnormalities

- ID: D000000013

- Term: Congenital Abnormalities

- ID: D000019465

- Term: Craniofacial Abnormalities

### Condition Browse Module - Browse Branches

- Abbrev: BC05

- Name: Musculoskeletal Diseases

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16357

- Name: Synostosis

- Relevance: HIGH

- As Found: Synostosis

- ID: M6613

- Name: Craniosynostoses

- Relevance: HIGH

- As Found: Trigonocephaly

- ID: M7587

- Name: Dysostoses

- Relevance: LOW

- As Found: Unknown

- ID: M5126

- Name: Bone Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5127

- Name: Bone Diseases, Developmental

- Relevance: LOW

- As Found: Unknown

- ID: M12097

- Name: Musculoskeletal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12

- Name: Congenital Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M12096

- Name: Musculoskeletal Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M21420

- Name: Craniofacial Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: T1638

- Name: Craniosynostosis

- Relevance: LOW

- As Found: Unknown

- ID: T5091

- Name: Saethre-Chotzen Syndrome

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000013580

- Term: Synostosis

- ID: D000003398

- Term: Craniosynostoses

### Misc Info Module

- Version Holder: 2024-05-24
