sickle-cell disease vaso-occlusive crisis
Conditions
Interventions
The patients will receive sevuparin or placebo via continuous infusion.
The duration of the infusion is at least 48 hours.
The maximum duration of infusion is 7 days.
The study medication dose is 18
ischemic organ damage
sevuparin infusion
sickle-cell disease
vaso-occlusive crisis
Sponsors
Modus Therapeutics AB
Eligibility
Age
12 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Sign a written informed consent. 2. Male or female, age 12 - 50 years. 3. Diagnosis of sickle cell disease, types HbSS, HbSC, Hb O Arab, HbSß0-thalassemia or HbSß+-thalassemia (SCD type to be confirmed by HPLC confirmed or other method of comparable reliability durin the study, if confirmation is not available at time of inclusion). 4. Subjects admitted for an acute, painful VOC to be treated / or treated with parenteral opiod analgesia at the time of admission. VOC is defined as an episode of pain that led to a clinic or emergency department visit, and cannot be explained except by SCD. Please note: Study treatment should start as soon as possible and at the latest within 24 hours from the time of the decision to hospitalize the subject. 5. Expectancy of the need for hospitalization for at least 48 hours. 6. Be at least 1 year postmenopausal, surgically sterile, or if WOCBP use an effective method of birth control during study drug administration and one month following treatment completion.
Exclusion criteria
Exclusion criteria: 1. Severe hepatic failure/disease, or liver enzyme tests (AST and ALT) above 2 times the upper limit of normal (ULN) range, or clinically significant impairment of liver function due to HBV, HCV or other liver diseases. 2. Conjugated (direct) bilirubin 3 fold above ULN. 3. History of clinically significant bleeding in vital organs (not due to relevant trauma), or pathological bleeding. 4. Current clinically significant bleeding, as judged by the investigator 5. Current use of ASA, anti-platelet therapy, anticoagulant therapy and prophylactic and therapeutic LMWH or un-fractioned heparin. 6. APTT above normal range, and INR above 1.4. 7. A platelet count 35 9. Subjects with more than 5 hospitalizations for VOC during the last 6 months (to exclude subjects with exacerbations of chronic pain rather than true vaso-occlusion). 10. Evidence of acute SCD complications other than VOC at screening (CVA, ACS, multi-organ failure). 11. The use of strong opiods for >3 consecutive days during the last 15 days before presenting to the hospital. 12. History of chronic drug abuse. 13. Renal dysfunction (GFR 450 msec (for details please see Section 8.3.3.) 16. History of a clinically significant drug allergy to heparin, LMWH*s, or Sevuparin. 17. Use of any investigational agent during the 30 days prior to the first dose. 18. For females: pregnancy, lactating or intention of becoming pregnant within the next 40 days. 19. Evidence of clinically significant disorders that might interfere with the study aim or safety of the subject, as judged by the Investigator: e.g. neurological, psychiatric (depression, psychosis or schizophrenia), cardiovascular (including arrhythmia), pulmonary, metabolic, gastrointestinal, endocrine diseases, coagulation or malignancies.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint: Time from the start of sevuparine infusion until resolution of crisis/episode is defined as fulfilment of the following two criteria: a. freedom from parental opioid use (in preceding 8 hours) b. readiness for discharge as judged by the subject or physician | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints: The secondary efficacy endpoints include assessment and comparison between the 2 treatment groups on the following parameters: 1. Frequency and pattern of treatment emergent adverse events (TEAEs). 2. Time to discharge (number of hours between the first study drug dose given and discharge). 3. Time to readiness for discharge, as judged by the subject or investigator (number of hours between the first study drug dose given and time point at which subjects feels readiness or investigator judges readiness for discharge from the hospital). The assessment will be done every 4 hours during awake time, staring from the time when the subject has been without parenteral opioids for 8 hours. 4. Time to discontinuation of IV opiods (number of hours between the first study drug dose given and discontinuation of opioids). 5. Time from start of infusion to 25%, 50% and 75% of subjects achieving VOC resolution. 6. Proportion of subjects with VOC resolution achieved at 24, 48, 72, 96 and 120 hours. 7. Clinical Global Impression of Change, measured once daily starting on day 3 until VOC resolution. 8. Patient Global Impression of Change, measured once daily starting on day 3 until VOC resolution. 9. Pain intensity assessment on VAS from the start of study treatment (first assessment within 30 minutes prior to infusion treatment) and thereafter every 4 hours during awake time, until VOC resolution. 10. Duration of severest pain, defined as time to a 30% reduction in VAS pain score from baseline (maintained during 8 hours) . 11. Amount of parenteral opioids (accumulated opioid consumption) until VOC resolution. 12. Amount of parenteral opioids (accumulated opioid consumption as average per 24h after first dose of study drug) until VOC resolution. 13. Re-occurrence of hospitalisation for VOC within 2 days, or 28 days from resolution of first VOC. 14. PK characteristics of Sevuparin administration as a continuous IV infusion (subgro | — |
Countries
The Netherlands
Outcome results
None listed