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Procedure Outcome Predictor (POP) Using the Complement Cascade (CPOP)

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ClinicalTrials.gov Identifier: NCT02531789
Recruitment Status : Completed
First Posted : August 24, 2015
Last Update Posted : August 24, 2015
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:
Current post-operative monitoring of patient recovery consists measuring two blood markers C-reactive protein (CRP) and White Blood Cell Count (WBC). However, these are slow to respond to the onset of infection. However, monitoring the absolute levels of the proteins in the three pathways of the complement cascade should provide a faster and better predictor of patient recovery. The investigators propose a pilot trial to measure concentrations of Complement Cascade (CC) activation biomarkers in the blood over a time course around operations of major abdomino-pelvic surgery involving a bowel resection. Further, analysis of the differential CC pathway activation should identify the onset of recovery complications before clinical symptoms present and potentially identify the causes allowing the clinicians to target therapies.

Condition or disease Intervention/treatment
Colorectal Surgical Procedure Outcomes Other: Observation

Detailed Description:

The proposed study is a pilot study on a cohort of participants recruited from routine elective colorectal surgery at RD&E. The pilot trial will collect blood over a time course for a patient to record blood plasma levels of Complement proteins peri-operatively from admission to discharge. The assay schedule is detailed in Table 1 below. The trial will perform additional CC activation tests on routine blood samples taken during the patient's stay in hospital. In addition 4 trial samples will be taken at time intervals that will capture the impulse response of the patient's CC. Sample analysis will be performed in parallel in the clinical chemistry laboratory for laboratory for assays of CRP and the complement proteins C3 and C4. The additional trial assays will be performed on the MSD platform on loan for the period of the trial.

Table 1Blood Sample Assay Schedule Time Point Time of Test Routine Test Additional Trial Test Trial Assays Day Timings 0 t = -1 Pre-admission clinic CONSENT ROUTINE CRP, LFTs, FBC, Amylase, Coag, G&S C4, C5, IgG C3dg, C4d, Bb, TCC, t =-1 day 2 Pre-operatively t = 0 Under anaesthesia Trial Sample NO.1 C4, C5, IgG C3dg, C4d, Bb, TCC, CRP t = 0 9:30 hrs 3 t =1 hr Under anaesthesia Knife-to-skin plus 30 mins Trial Sample NO.2 C4, C5, IgG C3dg, C4d, Bb, TCC, CRP 10.30 hrs 4 t = 2 - 4 hrs immediately post surgery ROUTINE C4, C5, IgG C3dg, C4d, Bb, TCC, CRP 1330hrs (equivalent to t +4hrs) 5 t = 8 hrs Trial Sample NO. 3 C4, C5, IgG C3dg, C4d, Bb, TCC, CRP 17:30 hrs 6 t = 12 hrs Trial sample NO. 4 C4, C5, IgG C3dg, C4d, Bb, TCC, CRP 21:30 hrs 7 t = 24 hrs ROUTINE C4, C5, IgG C3dg, C4d, Bb, TCC, CRP 09:30 hrs 8 t = 36 hrs ROUTINE C4, C5, IgG C3dg, C4d, Bb, TCC, CRP 21:30 hrs 9 t = 48 hrs

Some Patients Discharged

Complications Develop ROUTINE C4, C5, IgG C3dg, C4d, Bb, TCC, CRP t = x1 Routine Tests as these occur C4, C5, IgG C3dg, C4d, Bb, TCC, CRP t = x2 Routine tests as these occur C4, C5, IgG C3dg, C4d, Bb, TCC, CRP 10 Discharge

The assays deployed for the pilot trial the current biomarkers of C activation panel are C3dg, C4d, Bb, TCC and the acute phase marker, CRP. The TCC assay has been designed in Cardiff (by Prof Morgan a collaborator of Prof Shaw) and the investigators have extensive experience in the design of C protein assays. For the target biomarkers antibodies to neo-antigens that are revealed post enzymatic cleavage or complex formation will be used as capture antibodies on the surface of the MSD platform. The C proteins are then detected with polyclonal antibodies provided by Prof Morgan in Cardiff and labelled with a ruthenium tagged antibody. Whole EDTA-stabilised plasma is then incubated in the 96-well format; all 5 assays, including calibration curves, are run simultaneously. Electroluminescence from the ruthenium complex is collected and quantified automatically. Absolute measurements of C proteins will be performed using standardised fully activated serum which contains a constant amount of activation products from all complement pathways. The serum is available through Prof Morgan's collaboration with the 'Complement Standardization Group'. C activation relative to this standard can then be determined. This work will lead to an array of C activation markers that will be tested against the patient cohort. This array including some of the other pathway markers may ultimately become the basis of a routine clinical test.


Study Design

Study Type : Observational
Actual Enrollment : 45 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Procedure Outcome Predictor (POP) Using the Complement Cascade
Study Start Date : November 2010
Primary Completion Date : February 2011
Study Completion Date : February 2011
Groups and Cohorts

Group/Cohort Intervention/treatment
Observation
45 patients receiving elective colorectal surgery
Other: Observation
C3, C4, CRP, and the dilution marker total IgG, together with C3dg, TCC and Bb will be measured over a high-sampling frequency time course t=-1 (admission), 0 (induction), 2,4,8,16, 24, 36 and 48 hours.


Outcome Measures

Primary Outcome Measures :
  1. Assessment of the Complement Activation with descriptive statistics to establish the size of an effect for a larger prospective cohort study [ Time Frame: 5 days ]
    The study will determine Complement Cascade activation for a cohort of 45 patients receiving elective colorectal surgery. C3, C4, CRP, and the dilution marker total IgG, together with C3dg, TCC and Bb will be measured over a high-sampling frequency time course t=-1 (admission), 0 (induction), 2,4,8,16, 24, 36 and 48 hours.


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
45 patients receiving elective colorectal surgery
Criteria

Inclusion Criteria:

  • Elective surgery list of pelvic oncology surgeons

Exclusion Criteria:

  • Unable/unwilling to provide informed consent
  • Pregnant women
  • Under 18 years of age
  • Pre-existing active infection
  • Diabetic
  • Inflammatory bowel disorders
  • Immunosuppressed
  • Immunosuppression or steroid treatment within the last 12 months
  • Learning disability or mental health problems
  • Non-English speakers
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02531789


Sponsors and Collaborators
University of Exeter
Royal Devon and Exeter NHS Foundation Trust
Investigators
Principal Investigator: Andrew M Shaw, PhD University of Exeter
More Information

Responsible Party: University of Exeter
ClinicalTrials.gov Identifier: NCT02531789     History of Changes
Other Study ID Numbers: 1011/115491
First Posted: August 24, 2015    Key Record Dates
Last Update Posted: August 24, 2015
Last Verified: August 2015

Additional relevant MeSH terms:
Complement System Proteins
Immunologic Factors
Physiological Effects of Drugs