Complex Regional Pain Syndrome MedDRA version: 14.1 Level: LLT Classification code 10049475 Term: Chronic pain System Organ Class: 100000004867
Conditions
Interventions
Trade Name: Intratect
Product Name: Human normal immunoglobulin for intravenous use (IVIg)
Pharmaceutical Form: Infusion
INN or Proposed INN: Human norm
Sponsors
University of Liverpool
Walton Centre NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of Complex Regional Pain Syndrome I or II according to Budapest research criteria (appendix 5) (22). 2. Disease duration of 1-5 years and a mean pain intensity on an 11-point (0-10) Numeric Rating Scale (NRS) over the first seven daily entries after screening within a pre-defined range (see section 9 for details of pain thresholds for eligibility) 3. Failure to respond (poor efficacy or unacceptable side effects) to drugs recommended for the treatment of neuropathic pain (23), including pregabalin or gabapentin, a tricyclic antidepressant, and mild and strong opioids (where not contraindicated or refused by the patient). 4. Previous specialised pain physiotherapy (24), including desensitisation techniques, and either mirror therapy (25) or graded motor imagery treatment (26), or both (where not contraindicated or refused by the patient). 5. Willingness to confirm the use of adequate birth control while on the trial will be required in pre menopausal women without evidence for an inability to become pregnant. 6. Willingness to not start any other treatment for during the parallel part of the trial 7. Age 18 years and above Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 108 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Any individuals meeting any of the following will be excluded from the study: 1. Other significant chronic pains, which in the view of the study doctor may make assessment of the pain arising from CRPS difficult, 2. If the patient recently started a new therapy for CRPS, which in the view of the study doctor may change the patient’s pain level during the time of participation in the trial. 3. Unstable medical conditions 4. Litigation. Patients in litigation will be excluded only if conclusion of that litigation is imminent during the course of the study. 5. Pregnant or breastfeeding patients. 6. Complete IgA deficiency 7. Rare contraindications to IVIg therapy as per summary of product characteristics (SmPC) 8. Receiving IVIg for other reasons, 9. Patients previously enrolled in CRPS IVIg/SCIG trials 10. Drugs or alcohol abuse 11. Psychiatric or mental health disorder which could in the judgement of the site investigator interfere with successful study participation 12. Unwillingness or inability to complete daily diaries, or inability to understand the questionnaires being used. 13. Cancer other than basal cell carcinoma within the last 5 years. However those patients who have received definitive treatment, such as curative surgery more than 6 months ago, with no known recurrence can be included. 14. A history of hypercoagulable or thrombophilic clotting abnormalities. 15. A history of thrombembolic events: ischaemic stroke, confirmed myocardial infarction, pulmonary embolism; deep venous thrombosis except where immobility related (e.g. after injury or operation). 16. Unstable angina. 17. Renal failure, or serum creatinine greater than 1.5 times the upper limit of normal at screening. 18. Any medical condition which in the opinion of the investigator would make it unsafe for the patient to participate or which would interfere with assessment of the outcome measures. 19. Participation in another interventional trial within 3 months of randomisation. Participation in non-interventional studies is not a reason for exclusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Diary data collected daily from day 6 to day 42 post randomisation;Main Objective: To gain, within 44 months, both definite proof of the clinical efficacy, and a more confident estimate of the effect size of low-dose IVIg treatment to reduce pain in patients with msCRPS.; Secondary Objective: To achieve better understanding of this technology, including: 1. effect stability with repeat administration 2. factors predicting a beneficial response 3. effects on additional outcome parameters including stimulus evoked pain, pain interference, quality of life, and short-term risk profile 4. Health economics evaluation 5. to create a resource of biological samples at the University of Liverpool for future CRPS serum autoantibody, and serum-substances research ;Primary end point(s): • The primary outcome is the average 24h pain intensity over 37 days, recorded in pain diary entries for the previous 24 hours collected on days 6 to 42 (day 1=day of first infusion). Consenting patients providing a mobile phone number will be prompted automatically by SMS daily from day 2-42 to enter their pain intensity into their diary. In addition return SMSs from the patient, with the daily NRS pain value will be automatically saved as backup for the paper diary. The paper diary score will override the texted diary score, however every effort will be made to resolve any discrepancies. In participating patients unexplained lack of a response over two or three days will prompt a phone call from the study nurse to confirm that there are no issues. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Secondary outcomes will be pain interference measured using the interference subscale of the Brief Pain Inventory(11)1,and quality of life measured using the Euroqol EQ-5D-5L(12). • All other outcomes are exploratory. List of measures to be used: • Screening pain diaries (average 24h pain intensity numeric rating scale (NRS) only) • Detailed daily (three items: pain unpleasantness(13), average 24h NRS pain intensity, last 24h sleep quality (14))-and simplified weekly (weekly NRS pain intensity) pain diaries • Adverse events • Brief Pain Inventory- (diagram, worst pain intensity, and interference scales only) (11) • Concomitant medications • Concomitant therapies • Patient weight • Skin temperature measured with a surface thermometer • Limb volume measured with a water-bath technique • EQ-5D (5 Item)(12) • Expectations from treatment (15) • Functional items and fatigue suggested by-, and developed together with patient group (5 scales) • Patient Global Impression of change (16) • Hospital Anxiety and Depression Scale (17) • Health and Social care utilisation • Limb Exam recording Budapest CRPS signs, and any additional abnormalities on inspection, and sensory (cotton wool, pinprick, cold-fork) and motor (observation of active range) examination • McGill(18) • Quantitative Sensory Testing in 40 patients with stimulus evoked pain, excepting thermosensitivities (only in three trial centres) • Sullivan’s Pain Catastrophising Scale (19) • Time trade-off (20) • Work interference (Stanford Presenteeism Scale) (21) ; Timepoint(s) of evaluation of this end po | — |
Countries
United Kingdom
Contacts
Public ContactCaroline Murphy
King's College London
Outcome results
None listed