Investigation of Tetralogy of Fallot in Neonates

NCT06822400 | Recruiting DMC

• 1 other identifier: 20241226
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Child health serves as the foundation for overall public health, with neonatal mortality recognized globally as a comprehensive indicator of national health standards and societal advancement. The Healthy Children Action Improvement Plan (2021-2025) sets a national target to reduce neonatal mortality in China to below 3.1‰. Congenital heart disease (CHD), the most prevalent congenital defect among neonates, constitutes a significant cause of disability and premature death in the Chinese population. Annually, approximately 70,000-80,000 neonates are born with CHD, among whom nearly 10,000 present with critical congenital heart disease (CCHD). Postnatal manifestations of CCHD often include cyanosis, hypoperfusion, and respiratory distress, with untreated cases resulting in approximately 50% mortality. CCHD is one of the leading causes of infant death. Tetralogy of Fallot (TOF), the most common form of CCHD, accounts for a substantial proportion of cyanotic congenital heart diseases. It is characterized by four anatomical abnormalities: ventricular septal defect, pulmonary stenosis, overriding aorta, and right ventricular hypertrophy. These structural defects disrupt intracardiac blood flow, reduce arterial oxygen saturation, and result in cyanosis and other related symptoms. Untreated TOF leads to significant health issues early in life, including growth retardation, recurrent hypoxic episodes, heart failure, and increased susceptibility to infections. Long-term survival is markedly reduced, with only a small proportion surviving into adulthood. Thus, surgical intervention is pivotal for improving outcomes in TOF(Tetralogy of Fallot) patients. Despite advances in medical technology yielding satisfactory early outcomes, long-term prognosis following TOF correction remains a challenge. Historically, surgical strategies emphasized complete relief of right ventricular outflow tract obstruction, often at the expense of pulmonary valve function. Recent studies, however, highlight the critical role of preserving pulmonary valve function in improving long-term outcomes, as pulmonary valve dysfunction is a leading cause of late right ventricular failure and reintervention. Additionally, surgical approaches, whether via atrial or ventricular access, have inherent advantages and limitations, but neither can fully eliminate the risk of postoperative arrhythmias associated with TOF's anatomical complexity and surgical impact. These issues underscore the necessity for further advancements in long-term management strategies. Surgical correction of TOF in a single-stage procedure has become standard practice, with the timing of surgery progressively shifting to earlier ages-from school age in the 1990s to the current standard of 3-6 months of age. This timing ensures sufficient weight and organ maturity to withstand the complexities of cardiac surgery. However, in clinical practice, significant challenges persist, including: (1) Deterioration during the waiting period, during which patients may experience recurrent hypoxic episodes, inadequate weight gain, and exacerbated pulmonary vascular underdevelopment, thereby complicating definitive surgery and increasing perioperative risk. (2) Developmental delays due to chronic hypoxemia and heart failure, potentially leading to neurological deficits and pulmonary hypertension, adversely affecting cognitive and motor development. Neonatal repair, performed within 28 days of life, may mitigate these challenges by restoring normal circulatory physiology at the earliest possible stage. International guidelines endorse neonatal TOF repair for capable centers, citing the potential for enhanced clinical benefits and superior prognoses. Clinical observations at our center indicate several advantages of neonatal TOF repair, including reduced intraoperative bleeding, cleaner surgical fields, and better pulmonary vascular development. These benefits may be attributed to the regenerative potential of neonatal myocardial cells and the absence of prolonged pathological circulatory states, which otherwise exacerbate anatomical abnormalities. Early intervention may reduce right ventricular fibrosis and pulmonary vascular pathology, thereby improving long-term outcomes. With advancements in surgical techniques and perioperative care, neonatal TOF repair has become a routine practice at our center, with over 100 cases performed annually for two consecutive years. This success is supported by an integrated prenatal-to-postnatal care model, establishing a comprehensive treatment framework. Given this context, the investigators propose a multicenter, randomized controlled trial (RCT) to compare the safety and efficacy of neonatal and infant TOF repair. This study aims to provide high-quality evidence for clinical practice, determine optimal surgical timing, and enhance overall survival rates and quality of life for TOF patients.

Conditions

Tetralogy of Fallot (TOF); Pulmonary Stenosis; Ventricular Septal Defects (VSD); Double Outlet Right Ventricle

Keywords

Neonatal; Infant; RCT; surgery

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events(mortality)

  All-cause mortality within 30 days postoperatively, encompassing cardiovascular and non-cardiovascular causes.

  up to 30 days

• Rate of re-intervention 12 months after surgery

  Reoperation rate within 12 months postoperatively based on defined criteria, excluding in-hospital reinterventions.

  up to 12 months

Secondary Outcomes (17)

• Perioperative situation

  during surgery

• Perioperative situation

  during surgery

• Perioperative situation

  up to 720 hours

• Perioperative situation

  up to 720 hours

• Perioperative situation

  up to 30 days

Study Arms (2)

intervention group

ACTIVE COMPARATOR

Procedure: corrective surgery within 28 days of birth

control group

PLACEBO COMPARATOR

Procedure: corrective surgery between 3-6 months of age

Interventions

corrective surgery within 28 days of birth PROCEDURE

Participants will be randomized into two groups with a 1:1 allocation: Intervention Group: Neonates undergoing surgical correction of TOF within 28 days of birth.

intervention group

corrective surgery between 3-6 months of age PROCEDURE

Participants will be randomized into two groups with a 1:1 allocation: Control Group: Infants undergoing surgical correction of TOF between 3-6 months of age

control group

Eligibility Criteria

• Age: 1 Minute - 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Clinical diagnosis of TOF's Disease. Full-term neonates aged ≤28 days. Birth weight of all eligible male or female patients \>2.5 kg. All included study participants must be able to give an informed consent

You may not qualify if:

• Preterm infants . Coexisting complex cardiac anomalies. Severe TOF with pulmonary artery hypoplasia , recurrent hypoxic episodes , or conditions warranting palliative or single-ventricle repair.
• Extra-cardiac anomalies, including genetic or chromosomal abnormalities. Neonatal bronchopulmonary dysplasia. Deteriorating conditions in the control group precluding surgery by 3 months of age.
• Parental refusal to participate in the clinical trial.

Sponsors & Collaborators

• Beijing Anzhen Hospital: lead
• Children's Hospital of Fudan University: collaborator
• Suzhou University Affiliated Children's Hospital: collaborator
• Shenzhen Children's Hospital: collaborator
• West China Second University Hospital: collaborator

Study Sites (1)

Beijing Anzhen Hospital

Beijing, Beijing Municipality, 100013, China

RECRUITING

MeSH Terms

Conditions

Tetralogy of Fallot; Pulmonary Valve Stenosis; Heart Septal Defects, Ventricular; Double Outlet Right Ventricle

Interventions

Parturition; Aging

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Valve Diseases; Ventricular Outflow Obstruction; Heart Septal Defects; Transposition of Great Vessels

Intervention Hierarchy (Ancestors)

Pregnancy; Reproduction; Reproductive Physiological Phenomena; Reproductive and Urinary Physiological Phenomena; Growth and Development; Physiological Phenomena

Central Study Contacts

Qiang Wang Prof Beijing Anzhen Hospital,Capital Medical University

CONTACT

8613811548581; wq.cory@163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2025
• First Posted: February 12, 2025
• Study Start: March 1, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2028
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)