Perfusion Pressure Cerebral Infarction Trial (PPCI)

Postoperative Cognitive Dysfunction Clinical Trial

— PPCI  

Official title:

The Importance of Mean Arterial Pressure During Cardiopulmonary Bypass to Prevent Cerebral Complications After Cardiac Surgery - a Randomised Clinical Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02185885
• Other study ID #: H-3-2013-110
• Secondary ID: E-22329-014142,
• Status: Completed
• Phase: N/A
• First received: July 7, 2014
• Last updated: April 8, 2016
• Start date: July 2014
• Est. completion date: April 2016

Study information

• Verified date: April 2016
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: The Regional Committee on Biomedical Research EthicsDenmark: Danish Dataprotection Agency
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 197
• Est. completion date: April 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cognition Disorders
• Embolic Stroke
• Postoperative Cognitive Dysfunction

Intervention

Procedure:
• Increased bloodpressure during CPB.

Locations

Country	Name	City	State
Denmark	Department of Cardiothoracic Surgery 2152 and Department of Cardiothoracic Anesthesiology 4142, Rigshospitalet / Copenhagen University Hospital	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Danish Heart Foundation

Country where clinical trial is conducted

Denmark, 

References & Publications (1)

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. Erratum in: Lancet 1998 Jun 6;351(9117):1742. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	GAMPT BCC200 count	The GAMPT BCC200 is integrated into the heart-lung-machine (HLM), and through the use of ultrasound Doppler techniques, detection of gaseous micro-emboli (GME, volume between 5-500 µl) is enabled. The system can be used to quantify the GME that pass from the HLM into the bloodstream of the patient.	End of cardiopulmonary bypass procedure	No
Primary	Total volume of new ischemic cerebral lesions	The total volume of new ischemic cerebral lesions (sum in mL) assessed by diffusion-weighed-magnetic resonance imaging conducted preoperatively and again once postoperatively on day 3 to 6.; The analysis will be adjusted for the randomization stratification variables age and type of surgery.	6 days	No
Secondary	Total number of new ischemic cerebral lesions	The total number of new ischemic cerebral lesions (sum in mL) assessed by diffusion-weighed-magnetic resonance imaging conducted preoperatively and again once postoperatively on day 3 to 6.	6 days	No
Secondary	Magnetic resonance spectroscopy - change from baseline N-acetylaspartate-creatine (NAA/Cr) ratio at day 6	Diffuse cerebral injury is investigated using Single-Voxel Magnetic Resonance Spectroscopy (MRS) in grey and white cerebral matter and expressed as the difference in N-acetylaspartate-creatine (NAA/Cr) ratio between a scan conducted preoperatively and one conducted postoperatively on day 3 to 6.	6 days	No
Secondary	Magnetic resonance spectroscopy - change from baseline MRS Choline-creatine (Cho/Cr ratio) at day 6	Diffuse cerebral injury is investigated using Single-Voxel Magnetic Resonance Spectroscopy (MRS) in grey and white cerebral matter and expressed as the difference in Choline-creatine (Cho/Cr ratio) between a scan conducted preoperatively and one conducted postoperatively on day 3 to 6.	6 days	No
Secondary	Postoperative cognitive dysfunction (POCD) - change from baseline neuropsychological test performance at day 5-8	The presence of cognitive dysfunction is evaluated preoperatively and on day 5-8 using the following collection of specific tests each time: "Visual Verbal Learning test", "Concept Shifting test", "Stroop Colour Word Interference test" and "Letter Digit Coding test".; Cognitive dysfunction is defined as a deterioration corresponding to a Z-score > 2 (as defined by the ISPOCD group).	5-8 days	No
Secondary	Postoperative cognitive dysfunction (POCD) - change from baseline neuropsychological test performance at 3 months	The presence of cognitive dysfunction is evaluated preoperatively and 3 months postoperatively using the following collection of specific tests each time: "Visual Verbal Learning test", "Concept Shifting test", "Stroop Colour Word Interference test" and "Letter Digit Coding test".; Cognitive dysfunction is defined as a deterioration corresponding to a Z-score > 2 (as defined by the ISPOCD group).	3 months	No
Secondary	Peak value of biochemical markers of brain injury	Blood samples will be drawn at 4 different time points during the admission. Serum concentration and time course of the following markers of brain injury will be assessed: Phosphorylated Neurofilament Heavy Protein (pNfH), Glial Fibrillary Acidic Protein (GFAP), Matrix Metallopeptidase 9 (MMP-9) and Ubiquitin C-terminal Hydrolase 1 (UCH-L1).	Prior to surgery on day 1 and 24 hours, 48 hours and 6 days after surgery	No
Secondary	Near Infrared Spectroscopy (NIRS) - lowest value	Near Infrared Spectroscopy (NIRS) NIRS values from the right and left frontal lobes of the brain will be continuously monitored during the intraoperative period and saved for later analysis. The NIRS monitor will be hidden and muted during the procedure.	End of surgery	No
Secondary	Near Infrared Spectroscopy (NIRS) - total time below 25% of the baseline value on right and left side	Near Infrared Spectroscopy (NIRS) NIRS values from the right and left frontal lobes of the brain will be continuously monitored during the intraoperative period and saved for later analysis. The NIRS monitor will be hidden and muted during the procedure.	End of surgery	No
Secondary	Change from baseline performance at neurological examination day 6	New neurological deficits are assessed by performing an objective, clinical neurological examination.	6 days	No