An observational study in Acute Appendicitis, sponsored by University of Exeter. Completed at 1 site in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-03-01.
Sponsored by University of Exeter · Observational
Acute appendicitis is a common condition requiring urgent surgery but is often difficult to distinguish from other non-surgical conditions such as urinary infections, pelvic inflammatory disease and non-specific abdominal pain. Delay in diagnosis can result in significant morbidity and potential mortality. Currently, there is no one diagnostic test available and raised inflammatory markers such as C-reactive protein (CRP) and White Blood Count (WBC) along with an evolving clinical picture, help guide management. However, these markers are slow to respond to inflammation and are non-specific for appendicitis. The Complement cascade is an immune response to inflammation and infection involving three pathways which activate a number of proteins in the blood. Monitoring the absolute levels of these proteins should provide a faster and differential diagnostic test. The investigators propose a pilot trial to measure concentrations of Complement cascade activation biomarkers in the blood during hospital admissions for acute right lower abdominal pain, a symptom of appendicitis. Further, analysis of the differential Complement cascade pathway activation could potentially identify underlying pathology allowing the clinicians to target therapies.
The proposed study is a pilot study on a cohort of participants recruited at emergency admission with acute right iliac fossa pain (right lower abdominal pain) to the Royal Devon \& Exeter Hospital Accident \& Emergency department. The pilot trial will collect one urine sample on admission and blood over a time course for each patient to record blood plasma levels of Complement proteins during hospital admissions with suspected appendicitis. The assay schedule is detailed in Table 1 below. The trial will perform additional Complement cascade activation tests on routine blood samples taken during the patient's stay in hospital. In addition 3 trial samples will be taken at time intervals that will capture the early Complement cascade response. Those patients going onto surgery will have a total of 5 additional trial samples taken, with 2 samples taken intra-operatively whilst under anaesthesia. From our previous experience in a similar pilot study CPOP (Complement cascade Predictors of Procedural Outcome), the investigators have introduced a blood taking 'curfew window' in which trial sample No. 2 \& 3 must not take place between the hours of midnight and 0600 hrs. This is to incorporate the wishes of patients and improve compliance with the study. Sample analysis will be performed in parallel in the clinical chemistry laboratory for assays of CRP and the complement proteins C3 and C4. The additional trial assays will be performed by Prof Shaw's research post doctoral assistant in the clinical chemistry laboratory and in the Medical School. A fresh frozen urine sample will be acquired from the routine urine sample given on all admissions for RIF pain. This urine sample will be analysed for Complement activation products such as C3a and C5a. Diagnostic end points will be acquired through the routine management of these patients and accessed via the hospital imaging (PACS) and pathology (IHCS) reporting system. These will include appendix histology and microbiology, urinalysis, blood cultures, imaging and cervical swabs.
Table 1Blood Sample Assay Schedule Time Point Time of Test Routine Test Additional Trial Test Trial Assays Day Timings (example) PM Timings (example)
t = 0 Admission to A\&E
CONSENT ROUTINE:
WCC, CRP, LFTs, Amylase, Clotting. Urinalysis.
On attending clinicians discretion:
urine culture, blood cultures, cervical swabs, imaging: US, CT, mri. Serum: C3, C4, C3dg, compliment activation markers
Urine: compliment activation markers eg: C3a, C5a. 09:00 hrs 18:00 hrs
t =8h Trial Sample NO.2 C3, C4, C3dg, compliment activation markers 17:00hrs 02:00 hrs
No action: 'blood taking curfew'
t = 12 h Trial Sample NO. 3 C3, C4, C3dg, compliment activation markers 21:00 hrs 06:00 hrs
No action: 'blood taking curfew'
t = 71 h
Some Patients Discharged
Some patients for Laparoscopy ROUTINE C3, C4, C3dg, compliment activation markers 08:00hrs t = 62 h 08:00 hrs
If for surgery:
t = surg0
On Induction Trial Sample NO. 4 C3, C4, C3dg, compliment activation markers, CRP 09:00 hrs t = surg 0 21:00 hrs
t = surg 45 min
End of surgery Pathology: appendix specimen Microbiology: appendix swabs Trial Sample NO. 5 C3, C4, C3dg, compliment activation markers, CRP 09:45 hrs t = surg 60 min 22: 00 hrs
If readmitted within 14 days
tR=x d, y h(days, hours from t0) ROUTINE C3, C4, C3dg, compliment activation markers, CRP
The assays deployed for the CDAA pilot trial will include the current biomarkers of Complement consumption, C3 and C4, available in the clinical chemistry laboratory; in addition the investigators will use a panel of activation markers including C3dg, C4d, Bb and TCC that have been developed during the CPOP clinical trial. Prof Shaw's group now has extensive experience with the development, optimisation and internal auditing of the activation assays. The assay for the trial will be performed in Prof Shaw's laboratory in parallel with the clinical chemistry laboratory who will be responsible for producing aliquots from the plasma
419 studies on the registry are indexed under Appendicitis; 67 are open to participants now.
This study's enrollment of 70 is below the median of 200 across 151 observational studies indexed under Appendicitis.
Browse Appendicitis studies →University of Exeter is the lead sponsor of 140 studies on the registry; 25 are open to participants now.
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70 patients presenting with right Iliac Fosse pain
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Under 18 years unwilling to provide pregnant women diabetic immunosuppression or treatment within last 12 months learning disability Non-english speakers
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients presenting with right Iliac Fosse pain
Other: Observational
Complement cascade components C3, C4, iC3b and TCC serum concentrations were measured over the time course from t= admission, 4,8,12,23,47,71 hours or until discharge.
Complement Activation differential diagnosis of Acute Appendicitis in a patient cohort presenting with Right Iliac Fosse Pain
C3 and C4 plasma concentration were measured in units of g/L over the time course t= admission, 4,8,12,23,47,71 hours or until discharge. Activation measures were derived as C3 and C4 differences at time each time point compared with admission values to derive changes in concentration which were compared in patients with a positive pathology diagnosis of the excised appendix (AA Group) and patients with a negative pathology diagnosis of the excised appendix or those patients discharged without appendectomy (non-AA Group).
Time frame: up to 5 days
clinical Alvarado Score
The clinical Alvarado Score was derived for all patients on admission. Symptoms: Migration - score 1, Anorexia-acetone - score 1, Nausea-vomiting - score 1; Signs: Tenderness in the right lower quadrant - score 2, Rebound pain - score 1, Elevation in temperature - score 1; Laboratory: Leucocytosis - score 2, Shift to the left (i.e. neutrophils more than 75% of WCC) - score 1. Scores were compared in patients with a positive pathology diagnosis of the excised appendix (AA Group) and patients with a negative pathology diagnosis of the excised appendix or those patients discharged without appendectomy (non-AA Group).
Time frame: up to 5 days
The clinical Alvarado Score modified to include CRP > 5 mg/L - score 1
The clinical Alvarado Score modified to include CRP \> 5 mg/L - score 1and was derived for all patients on admission. Symptoms: Migration - score 1, Anorexia-acetone - score 1, Nausea-vomiting - score 1; Signs: Tenderness in the right lower quadrant - score 2, Rebound pain - score 1, Elevation in temperature - score 1; Laboratory: Leucocytosis - score 2, Shift to the left (i.e. neutrophils more than 75% of WCC) - score 1. Scores were compared in patients with a positive pathology diagnosis of the excised appendix (AA Group) and patients with a negative pathology diagnosis of the excised appendix or those patients discharged without appendectomy (non-AA Group).
Time frame: up to 5 days
Complement Activation Derived from C3dg
C3dg plasma concentrations were measured in units of micrograms/mL over the time course t= admission, 4,8,12,23,47,71 hours or until discharge. Activation measures were derived as C3 and C4 differences at time each time point compared with admission values to derive changes in concentration which were compared in patients with a positive pathology diagnosis of the excised appendix (AA Group) and patients with a negative pathology diagnosis of the excised appendix or those patients discharged without appendectomy (non-AA Group).
Time frame: up to 5 days
Complement Activation Terminal Cascade Complex
Terminal Cascade Complex plasma concentrations measured in units of ng/mL over the time course t= admission, 4,8,12,23,47,71 hours or until discharge. Activation measures were derived as C3 and C4 differences at time each time point compared with admission values to derive changes in concentration which were compared in patients with a positive pathology diagnosis of the excised appendix (AA Group) and patients with a negative pathology diagnosis of the excised appendix or those patients discharged without appendectomy (non-AA Group).
Time frame: up to 5 days
Complement Activation C3a in Urine
C3a concentrations in urine were measured in units of ng/mL over the time course t= admission, 4,8,12,23,47,71 hours or until discharge. Activation measures were derived as C3 and C4 differences at time each time point compared with admission values to derive changes in concentration which were compared in patients with a positive pathology diagnosis of the excised appendix (AA Group) and patients with a negative pathology diagnosis of the excised appendix or those patients discharged without appendectomy (non-AA Group).
Time frame: up to 5 days
C Reactive Protein Acute Phase Marker
C reactive protein serum concentrations were measured in units of mg/L over the time course t= admission, 4,8,12,23,47,71 hours or until discharge. Acute Phase measures were derived as C3 and C4 differences at time each time point compared with admission values to derive changes in concentration which were compared in patients with a positive pathology diagnosis of the excised appendix (AA Group) and patients with a negative pathology diagnosis of the excised appendix or those patients discharged without appendectomy (non-AA Group).
Time frame: up to 5 days
The record gives a start of Jan 2012, a primary completion of Oct 2014 and a completion of Oct 2014. It does not say whether these dates are actual or estimated.
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This study is completed, as verified in Feb 2018. You cannot join it, but the record below documents what was studied.
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