Clinical trial NCT02185885: Perfusion Pressure Cerebral Infarction Trial (PPCI)
Official title: The Importance of Mean Arterial Pressure During Cardiopulmonary Bypass to Prevent Cerebral Complications After Cardiac Surgery - a Randomised Clinical Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Embolic Stroke
Postoperative Cognitive Dysfunction
Keywords: Ischemic stroke
Embolic stroke
Postoperative Cognitive Dysfunction
Cardiac Bypass Surgery
Cardiac Anaesthesia
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Danish Heart Foundation
First posted: 2014-07-10
Enrollment: 197
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: STUDY HYPOTHESIS

In cardiac surgery the volume of perioperative cerebral infarctions can be reduced by increasing mean arterial pressure (MAP) during the cardiopulmonary bypass procedure.

BRIEF STUDY SUMMARY

Heart surgery using cardiopulmonary bypass (CPB) can be complicated by injury to the brain. Previous studies using brain scans have reported small stroke-like lesions in up to 51% of patients after cardiac surgery. However, only 1-6 % of patients have permanent symptoms of severe brain damage.

The majority of brain lesions seem to be caused by particulate matter (emboli) that wedge in blood vessels of the brain thereby compromising flow. In addition, insufficient blood flow to areas of the brain supplied by narrowed, calcified vessels may contribute. MAP during CPB usually stabilizes below the lower limit of cerebral autoregulation, which is accepted since sufficient total blood flow is guaranteed during CPB.

The aim of the PPCI trial is to investigate if increased MAP during CPB can prevent or reduce the extent of brain injury after cardiac surgery. A beneficial effect could result from reduced embolic injury through increased blood flow in collateral vessels and/or by increased blood flow in calcified arteries.

180 patients scheduled for cardiac surgery will be randomly allocated to increased MAP (70-80 mm Hg) or 'usual practice' (typically 45-50 mm Hg) during CPB, whereas CPB blood flow is intended equal and fixed in the two groups. Patients are examined before and 3-6 days after surgery with magnetic resonance imaging (MRI) brain scans, mental tests and by blood borne markers of brain injury.

If higher MAP during CPB is beneficial, a change of practice can easily be implemented in the clinical routine.

Detailed description: TRIAL DESIGN

The PPCI trial is a randomized, controlled, outcomes assessor and patient blinded, single-center superiority trial with two parallel groups in a 1:1 allocation ratio. The randomization will be stratified according to age (stratum 1 \< 70 years; stratum 2 ≥ 70 years) and type of surgery (stratum 1 - surgery involving the aortic and/or mitral valve; stratum 2 - surgery not involving these valves).

Eligibility criteria: Inclusion Criteria:

* ≥ 18 years of age.
* scheduled elective or subacute cardiac surgery with the use of CPB.
* type of surgery either coronary artery bypass grafting (CABG) and/or heart valve surgery (provided that the valve prosthesis used is MRI compatible).

Exclusion Criteria:

* a history of stroke.
* a history of reversible ischemic deficits (duration of symptoms 24-72 hours)
* a history of transitory ischemic attacks (duration of symptoms \< 24 hours)
* diagnosis of neurodegenerative disorders such as Alzheimers, Multiple Sclerosis etc.

Primary outcomes:
measure: Total volume of new ischemic cerebral lesions
timeFrame: 6 days
Secondary outcomes:
measure: Total number of new ischemic cerebral lesions
timeFrame: 6 days
measure: Magnetic resonance spectroscopy - change from baseline N-acetylaspartate-creatine (NAA/Cr) ratio at day 6
timeFrame: 6 days
measure: Magnetic resonance spectroscopy - change from baseline MRS Choline-creatine (Cho/Cr ratio) at day 6
timeFrame: 6 days
measure: Postoperative cognitive dysfunction (POCD) - change from baseline neuropsychological test performance at day 5-8
timeFrame: 5-8 days
measure: Postoperative cognitive dysfunction (POCD) - change from baseline neuropsychological test performance at 3 months
timeFrame: 3 months
measure: Peak value of biochemical markers of brain injury
timeFrame: Prior to surgery on day 1 and 24 hours, 48 hours and 6 days after surgery
measure: Near Infrared Spectroscopy (NIRS) - lowest value
timeFrame: End of surgery
measure: Near Infrared Spectroscopy (NIRS) - total time below 25% of the baseline value on right and left side
timeFrame: End of surgery
measure: Change from baseline performance at neurological examination day 6
timeFrame: 6 days
Other outcomes:
measure: GAMPT BCC200 count
timeFrame: End of cardiopulmonary bypass procedure
Locations:
city: Copenhagen
country: Denmark
facility: Department of Cardiothoracic Surgery 2152 and Department of Cardiothoracic Anesthesiology 4142, Rigshospitalet / Copenhagen University Hospital
Study officials:
affiliation: Rigshospitalet, Denmark
name: Jens C. Nilsson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Hanne B. Ravn, MD, DMSc
role: STUDY_CHAIR
References:
citation: Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, Langeron O, Johnson T, Lauven PM, Kristensen PA, Biedler A, van Beem H, Fraidakis O, Silverstein JH, Beneken JE, Gravenstein JS. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998 Mar 21;351(9106):857-61. doi: 10.1016/s0140-6736(97)07382-0.
citation: Vedel AG, Holmgaard F, Danielsen ER, Langkilde A, Paulson OB, Ravn HB, Rasmussen LS, Nilsson JC. Blood pressure and brain injury in cardiac surgery: a secondary analysis of a randomized trial. Eur J Cardiothorac Surg. 2020 Nov 1;58(5):1035-1044. doi: 10.1093/ejcts/ezaa216.
citation: Holmgaard F, Vedel AG, Rasmussen LS, Paulson OB, Nilsson JC, Ravn HB. The association between postoperative cognitive dysfunction and cerebral oximetry during cardiac surgery: a secondary analysis of a randomised trial. Br J Anaesth. 2019 Aug;123(2):196-205. doi: 10.1016/j.bja.2019.03.045. Epub 2019 May 17.
citation: Holmgaard F, Vedel AG, Lange T, Nilsson JC, Ravn HB. Impact of 2 Distinct Levels of Mean Arterial Pressure on Near-Infrared Spectroscopy During Cardiac Surgery: Secondary Outcome From a Randomized Clinical Trial. Anesth Analg. 2019 Jun;128(6):1081-1088. doi: 10.1213/ANE.0000000000003418.
citation: Holmgaard F, Vedel AG, Langkilde A, Lange T, Nilsson JC, Ravn HB. Differences in regional cerebral oximetry during cardiac surgery for patients with or without postoperative cerebral ischaemic lesions evaluated by magnetic resonance imaging. Br J Anaesth. 2018 Dec;121(6):1203-1211. doi: 10.1016/j.bja.2018.05.074. Epub 2018 Jul 26.
citation: Vedel AG, Holmgaard F, Rasmussen LS, Langkilde A, Paulson OB, Lange T, Thomsen C, Olsen PS, Ravn HB, Nilsson JC. High-Target Versus Low-Target Blood Pressure Management During Cardiopulmonary Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients: A Randomized Controlled Trial. Circulation. 2018 Apr 24;137(17):1770-1780. doi: 10.1161/CIRCULATIONAHA.117.030308. Epub 2018 Jan 16.
citation: Vedel AG, Holmgaard F, Rasmussen LS, Paulson OB, Thomsen C, Danielsen ER, Langkilde A, Goetze JP, Lange T, Ravn HB, Nilsson JC. Perfusion Pressure Cerebral Infarct (PPCI) trial - the importance of mean arterial pressure during cardiopulmonary bypass to prevent cerebral complications after cardiac surgery: study protocol for a randomised controlled trial. Trials. 2016 May 17;17(1):247. doi: 10.1186/s13063-016-1373-6.