Early Tracheostomy in Ventilated Stroke Patients 2

Background: According to United States data from the National Inpatient Sample, about 1.3% of 1.5 million patients (20,300) hospitalized with ischemic stroke from 2007-2009 underwent tracheostomy - while the number of tracheostomies performed for hemorrhagic stroke is unknown. Historically, mechanically ventilated patients with ischemic or hemorrhagic strokes have had poor functional outcomes, and care of such patients is extremely expensive. Effective interventions to improve survival, improve functional recovery, decrease costs, and increase cost-effectiveness are urgently needed. Early tracheostomy of selected medical and surgical patients allows for dramatically decreased sedation and analgesia, and is associated with improved outcomes. Preliminary data from a pilot study of early tracheostomy in patients with hemorrhagic or ischemic stroke suggest that such patients may also have improved survival and long-term functional outcomes, but a large, multicenter clinical trial is needed to confirm these findings.

Method: SETPOINT 2 is a prospective, randomized, controlled, outcome observer-blinded, multicenter, two-armed, comparative trial. Patients are randomized 1:1 to either the experimental group - who undergo percutaneous tracheostomy (PDT) as soon as feasible and within 5 days after intubation ("early tracheostomy") or to the control group ("standard of care" group), in which PDT is performed after day 10 from intubation if the application of an in-house weaning protocol did not lead to successful extubation. Otherwise, no differences in intensive care treatment are intended, and each participating institution's standard operating procedures will be applied to ensure uniform management decisions in fields such as weaning, ventilation, analgesia and sedation, transfusion, and neurological monitoring and management. Blinding to the treatment assignment is impossible for treating physicians, patients and legal representatives as well as for most of the investigators. However, the primary endpoint of long-term outcome and causes of mortality will be assessed by trial-independent adjudicators blinded to the timing of tracheostomy.

The study started as an investigator initiated study which was conducted with limited external funding. Some funding (about 50 000 Euros) was provided from third party funds by the principal investigator and other foundations to provide for data management by the IMBI and other organizational aspects of the study. The principal investigator and the US co-principle investigator-David B. Seder, M.D.) together applied for research funding to several foundations and medical associations and in December 2016 received confirmation of funding from the Patient-Centered Outcomes Research Institute (PCORI). Based on this award, some additional endpoints (e.g. neuromonitoring, patient and family experience) were added as secondary endpoints in this study. The core version of this study remained unchanged. There will be no industry funding of the SETPOINT 2 study. This is not an investigation of any specific medical products or medications.

Inclusion criteria

• Age 18 years or older
• informed consent from legal representative
• non-traumatic cerebrovascular disease
• Estimated ventilation need for at least 2 weeks
• The clinical judgement of the attending neurointensivist
• principle indication for tracheostomy

Exclusion criteria

• Premorbid modified Rankin Score (mRS)>1
• Artificial ventilation for more than 4 days
• Severe chronic pulmonary disease requiring supplemental oxygen, or evidence of CO2 retention on admission serum analysis (HCO3≥30)
• Severe chronic cardiac disorder
• Any emergency situation compromising the patient's well-being or ability to undergo tracheostomy in the study time-frame
• Intracranial pressure (ICP) persistently > 25cmH2O
• Difficult airway management, anticipated problems with extubation / re-intubation,
• Need for a permanent surgical tracheostomy
• Contraindications for a percutaneous tracheostomy (see below)
• High oxygenation requirements: Positive end-expiratory pressure > 12, or fraction of inspired oxygen > 0.6)
• Pregnancy
• Participation in any other interventional trial
• Life expectancy < 3 weeks
• Patient/family unlikely to opt for at least 3 weeks of aggressive therapy prior to consideration of transition to comfort measures/discontinuation of life support measures