Cold Heart Study: A Randomized Pilot Trial of Surfactant Therapy

• ClinicalTrials.gov Identifier: NCT04181255
• Recruitment Status: Recruiting
• First Posted: November 29, 2019
• Last Update Posted: January 10, 2020
• Sponsor: University of Michigan
• Collaborator: Chiesi Farmaceutici S.p.A.
• Information provided by (Responsible Party): Steven Donn, M.D., University of Michigan

Study Description

Brief Summary:

This clinical trial is being done to see if giving surfactant (Curosurf®) will decrease the number of days that infants will need a breathing tube, decrease the days in the critical care unit and decrease the number of days needed in the hospital. The primary hypothesis for this study is that there will be fewer days needed on mechanical ventilation and improved lung compliance and pulmonary gas exchange.

Condition or disease	Intervention/treatment	Phase
Congenital Heart Disease; Hypoplastic Left Heart Syndrome	Drug: Curosurf; Drug: Sham	Phase 1

Detailed Description:

This study will enroll infants undergoing cardiothoracic surgery requiring deep hypothermic circulatory arrest (DHCA) at the University of Michigan's C.S. Mott Children's Hospital. Patients that are eligible will be randomized to receive either one dose surfactant or the sham (air) arm after the surgical procedure. Patients will be monitored for an additional 30 days after the breathing tube is removed. It is possible that subjects may be discharged prior to the last assessment, therefore for subjects who have been discharged a member of the study team will contact the parent (s) or legal authorized representative by telephone.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: The Cold Heart Study: A Randomized Pilot Trial of Surfactant Therapy Following Deep Hypothermic Circulatory Arrest During Cardiac Surgery
• Estimated Study Start Date: February 2020
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: December 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Curosurf	Drug: Curosurf; This arm will consist of a single dose of Curosurf (200 mg/kg) that will be given in the Pediatric Cardiothoracic Unit (PCTU) after surgery once the subject has reached a normalized body temperature.; Other Names: poractant alfa; surfactant
Placebo Comparator: Sham (air)	Drug: Sham; This arm will consist of a single dose of sham (air) that will be given through the endotracheal tube in the Pediatric Cardiothoracic Intensive Care Unit after surgery once the subject has reached a normalized body temperature.

Outcome Measures

Primary Outcome Measures :

1. Number of days of mechanical ventilation [ Time Frame: Throughout hospitalization (approximate average 5 days) ]
   This will be the number of days from intubation to the extubation date.
2. Number of days in the Pediatric Cardiothoracic Unit [ Time Frame: Approximately 11 days ]
   From time of admission until transfer out of the unit.
3. Number of post-operative hospital days [ Time Frame: Up to 1 year ]

Secondary Outcome Measures :

1. Total number of patients requiring thoracostomy tube placement for air leak not associated with standard post-operative management prior to extubation [ Time Frame: Approximately 1 week ]
   Post-surgery prior to extubation.
2. Total number of patients requiring high frequency ventilation (HFV) (High frequency oscillator ventilation or High frequency jet ventilation) [ Time Frame: Up to 1 year ]
   Post-surgery throughout hospitalization.
3. Total number of patients requiring extracorporeal membrane oxygenation (ECMO) for pulmonary failure [ Time Frame: Up to 1 year ]
   Post-surgery throughout hospitalization.
4. Changes in positive end-expiratory pressures post intervention [ Time Frame: Baseline to approximately 1 week ]
   After therapy until extubation.
5. Changes in peak inspiratory pressures post intervention [ Time Frame: Baseline to approximately 1 week ]
   After therapy until extubation.
6. Changes in dynamic lung compliance post intervention [ Time Frame: Baseline to approximately 1 week ]
   After therapy until extubation.
7. Changes in oxygen requirements post intervention [ Time Frame: Baseline to approximately 1 week ]
   After therapy until extubation.
8. Changes in oxygenation index (OI) post intervention [ Time Frame: Baseline to approximately 1 week ]
   OI is the product of mean airway pressure and fraction of inspired oxygen divided by the partial pressure of oxygen. After therapy until extubation.
9. Time to successful extubation readiness trials (ERT) post intervention [ Time Frame: Approximately 1 week ]

   Measured in hours until successful ERT, and then successful extubation. Not everyone who passes an ERT is immediately extubated (typically done once per day), so the plan is daily.

   Successful extubation is defined as remaining extubated for 48 hours.

Eligibility Criteria

• Ages Eligible for Study: up to 12 Weeks (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients less than or equal to 12 weeks of age with hypoplastic left heart syndrome (HLHS) undergoing cardiothoracic surgical correction (Norwood) requiring DHCA.
• Infants weighing 2500 grams or greater at the time of surgery.
• Written informed consent from parent(s) or legally appointed representative (LAR).

Exclusion Criteria:

• Patients who are less than 36 weeks Post Menstrual Age (PMA) at the time of surgical correction.
• Underlying craniofacial, airway or lung anomalies which could compromise administration of surfactant.
• Infants weighing less than 2500 grams at the time of the surgical correction.
• Mechanical ventilation for> 7 days prior to surgical correction.

Contacts and Locations

Contacts

Contact: Diane White; 734-615-7840; dfwhite@umich.edu

Contact: Steven Donn, MD; 734-232-0334; smdonnmd@umich.edu

Locations

United States, Michigan

University of Michigan; Recruiting

Ann Arbor, Michigan, United States, 48109

Contact: Diane White 734-615-7840 dfwhite@umich.edu

Sponsors and Collaborators

University of Michigan

Chiesi Farmaceutici S.p.A.

Investigators

• Principal Investigator: Steven Donn, MD; University of Michigan

More Information

• Responsible Party: Steven Donn, M.D., Professor Emeritus of Pediatrics, University of Michigan
• ClinicalTrials.gov Identifier: NCT04181255
• Other Study ID Numbers: HUM00160492
• First Posted: November 29, 2019
• Last Update Posted: January 10, 2020
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Steven Donn, M.D., University of Michigan:

Norwood procedure

Additional relevant MeSH terms:

Heart Diseases; Hypoplastic Left Heart Syndrome; Cardiovascular Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Pulmonary Surfactants; Poractant alfa; Respiratory System Agents