Perfusion Pressure Cerebral Infarction Trial (PPCI) (PPCI)

April 8, 2016 updated by: Jens C. Nilsson, Rigshospitalet, Denmark

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

197

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Denmark, DK-2100
        • Department of Cardiothoracic Surgery 2152 and Department of Cardiothoracic Anesthesiology 4142, Rigshospitalet / Copenhagen University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Increased bloodpressure during CPB
The cardiopulmonary bypass (CPB) procedure is conducted according to department guidelines with the modification that MAP is kept between 70 and 80 mm Hg. This is achieved by refract intravenous doses of phenylephrine to a total maximum of 2.0 mg, and after that continuous intravenous infusion of norepinephrine up to 0.4 μg/kg/min if necessary.
Procedure: Increased bloodpressure during CPB.
No Intervention: Regular bloodpressure during CPB
The cardiopulmonary bypass (CPB) procedure is conducted in accordance with departmental guidelines, where MAP is sought to be ≥ 45 mm Hg. This is achieved by refract intravenous doses of phenylephrine to a total maximum of 2.0 mg, and after that continuous intravenous infusion of norepinephrine up to 0.4 μg/kg/min if necessary.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total volume of new ischemic cerebral lesions
Time Frame: 6 days

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total number of new ischemic cerebral lesions
Time Frame: 6 days
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
Magnetic resonance spectroscopy - change from baseline N-acetylaspartate-creatine (NAA/Cr) ratio at day 6
Time Frame: 6 days
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
Magnetic resonance spectroscopy - change from baseline MRS Choline-creatine (Cho/Cr ratio) at day 6
Time Frame: 6 days
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
Postoperative cognitive dysfunction (POCD) - change from baseline neuropsychological test performance at day 5-8
Time Frame: 5-8 days

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
Postoperative cognitive dysfunction (POCD) - change from baseline neuropsychological test performance at 3 months
Time Frame: 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
Peak value of biochemical markers of brain injury
Time Frame: Prior to surgery on day 1 and 24 hours, 48 hours and 6 days after surgery
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
Near Infrared Spectroscopy (NIRS) - lowest value
Time Frame: End of surgery
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
Near Infrared Spectroscopy (NIRS) - total time below 25% of the baseline value on right and left side
Time Frame: End of surgery
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
Change from baseline performance at neurological examination day 6
Time Frame: 6 days
New neurological deficits are assessed by performing an objective, clinical neurological examination.
6 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
GAMPT BCC200 count
Time Frame: End of cardiopulmonary bypass procedure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rigshospitalet, Denmark

Collaborators

Danish Heart Foundation

Investigators

  • Principal Investigator: Jens C. Nilsson, MD, PhD, Rigshospitalet, Denmark
  • Study Chair: Hanne B. Ravn, MD, DMSc, Rigshospitalet, Denmark

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2014

Primary Completion (Actual)

January 1, 2016

Study Completion (Actual)

April 1, 2016

Study Registration Dates

First Submitted

July 7, 2014

First Submitted That Met QC Criteria

July 7, 2014

First Posted (Estimate)

July 10, 2014

Study Record Updates

Last Update Posted (Estimate)

April 11, 2016

Last Update Submitted That Met QC Criteria

April 8, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H-3-2013-110
  • E-22329-01 (Other Identifier: Rigshospitalet, project.no.)
  • 4142, PPCI (Other Identifier: Dep. of Cardiothoracic Anesthesiology)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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