Acute AppendicitisCDAANCT03450642
Complement Diagnosis of Acute Appendicitis
An observational study of Acute Appendicitis, run by University of Exeter at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Appendicitis
- What is being tested?
- Observational
- How many people
- 70 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2012to Oct 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 70 patients presenting with right Iliac Fosse pain
Who may be able to join
- Admission for right iliac fossa pain
Who cannot join
- Under 18 years unwilling to provide informed consent pregnant women diabetic immunosuppressed immunosuppression or steroid treatment within last 12 months learning disability Non-english speakers
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Royal Devon & Exeter Foundation NHS Trust
Exeter, Devon, EX2 5DW
About this study
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.
Read the detailed description
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 = 1-4 h CONSENT(if not previously obtained) 09:00 to 13:00 hrs 1800 to 22:00 hrs
- t = 4 h Trial Sample NO.1 C3, C4, C3dg,compliment activation markers 13:00 hrs 22:00 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 = 23 h ROUTINE C3, C4, C3dg, compliment activation markers 08:00hrs t = 14 h 08:00 hrs
- t = 47 h ROUTINE C3, C4, C3dg, compliment activation markers 08:00hrs t = 38 h 08:00 hrs
- 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
- t = x d, y h (days, hours from t0) Routine tests as they occur C3, C4, C3dg, compliment activation markers, CRP
- Discharge
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
- Conditions
- Acute Appendicitis
- Being tested
- Observational
- Medical subject headings
- Appendicitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ObservationalOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Observation | Patients presenting with right Iliac Fosse pain Receives: Other: Observational |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: up to 5 days
Secondary outcomes (6)
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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: up to 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2018
- Study startJan 2012
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute AppendicitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Exeter
- Sponsor type
- University, hospital or other
- Collaborators
- Royal Devon and Exeter NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Andrew M Shaw, PhD, Principal investigator, University of Exeter
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03450642
- Sponsor's protocol ID
- 1112/131544
- Acronym
- CDAA
- Status last verified
- Feb 2018
- First submitted
- 5 Aug 2015
- Last updated
- 1 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Complement Diagnosis of Acute Appendicitis
- ClinicalTrials.gov ID
- NCT03450642
- Acronym / sponsor ID
- CDAA / 1112/131544
- Conditions
- Acute Appendicitis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- University of ExeterUniversity, hospital or other
- Collaborators
- Royal Devon and Exeter NHS Foundation Trust
- Study start
- Jan 2012
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 1 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 = 1-4 h CONSENT(if not previously obtained) 09:00 to 13:00 hrs 1800 to 22:00 hrs
- t = 4 h Trial Sample NO.1 C3, C4, C3dg,compliment activation markers 13:00 hrs 22:00 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 = 23 h ROUTINE C3, C4, C3dg, compliment activation markers 08:00hrs t = 14 h 08:00 hrs
- t = 47 h ROUTINE C3, C4, C3dg, compliment activation markers 08:00hrs t = 38 h 08:00 hrs
- 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
- t = x d, y h (days, hours from t0) Routine tests as they occur C3, C4, C3dg, compliment activation markers, CRP
- Discharge
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
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Observation | – | Other: ObservationalPatients presenting with right Iliac Fosse pain |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 70 patients presenting with right Iliac Fosse pain
Key inclusion criteria (1 listed)
- Admission for right iliac fossa pain
Key exclusion criteria (1 listed)
- Under 18 years unwilling to provide informed consent pregnant women diabetic immunosuppressed immunosuppression or steroid treatment within last 12 months learning disability Non-english speakers
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ObservationalComplement 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. | Other | Observation |
Primary outcome
Complement Activation differential diagnosis of Acute Appendicitis in a patient cohort presenting with Right Iliac Fosse Pain
Time frame: up to 5 days
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).
6 secondary outcomes
clinical Alvarado Score
Time frame: up to 5 days
The clinical Alvarado Score modified to include CRP > 5 mg/L - score 1
Time frame: up to 5 days
Complement Activation Derived from C3dg
Time frame: up to 5 days
Complement Activation Terminal Cascade Complex
Time frame: up to 5 days
Complement Activation C3a in Urine
Time frame: up to 5 days
C Reactive Protein Acute Phase Marker
Time frame: up to 5 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew M Shaw, PhD principal investigator
University of Exeter
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Appendicitis, run by University of Exeter at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complement Activation differential diagnosis of Acute Appendicitis in a patient cohort presenting with Right Iliac Fosse Pain (time frame: up to 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2018.