The aim of the present *proof-of-principle* study is to test in patients suffering from AIHA whether co-administration of C1-inh improves the recovery of RBC transfusion by the inhibition of the activation of the classical pathway of complement. In…
ID
Source
Brief title
Condition
- Immune system disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
* improvement of the recovery of RBC transfusion- as defined as a decrease of
hemoglobin <1 g/dl (0.6 mmol/L) /24 hrs
* inhibition of complement activation and deposition on RBC via the classical
pathway of complement
* safety
Secondary outcome
* Inhibition of the pro-inflammatory response
Background summary
Autoimmune hemolytic anemia (AIHA) is characterized by premature destruction of
red blood cell (RBC) due autoantibodies directed to RBC antigens with or
without activation of the classical pathway of complement. Activation of the
classical pathway of complement by autoantibodies of the IgM isotype can lead
to life-threatening intravascular hemolysis with an acute consumption of oxygen
carriers, resulting in acute tissue hypoxia. However, the efficacy of
life-saving transfusion is severely compromised since the RBC autoantibodies
react with both recipient and donor RBCs, leading to a rapid destruction of
donor RBCs as well. C1-esterase inhibitor (C1-inh) is an efficient inhibitor of
the classical pathway of complement. C1-inh is being used for 30 years to treat
patients with hereditary angioedema. In addition, C1-inh is successfully used
in diseases caused by ischemia-reperfusion injury and sepsis. In all these
applications C1-inh turned out to have an excellent safety profile.
Because C1-inh is an efficient inhibitor of the classical pathway of complement
with an excellent safety profile we hypothized that C1-inh might inhibit
autoantibody mediated destruction of donor RBS in order to improve efficacy of
RBC transfusion.
Study objective
The aim of the present *proof-of-principle* study is to test in patients
suffering from AIHA whether co-administration of C1-inh improves the recovery
of RBC transfusion by the inhibition of the activation of the classical pathway
of complement. In addition, the effects of C1-inh on the pro-inflammatory
response in AIHA patients will be investigated.
Study design
This is a prospective, multicenter, national open label study to test the
efficacy of C1-inh to improve the efficacy of RBC transfusion in patients with
AIHA
Intervention
Patients will receive C1-inh: 6000 Units before the transfusion and thereafter
3000U, 2000U and 1000U every 12 hours
Study burden and risks
-
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
* Positive (*1+) monospecific antiglobulin test for C3b and/or C3d with/without
positivity for IgM OR strongly positive (*3+) monospecific antiglobulin test
for C3b and/or C3d with positivity for IgG
* Indication for a transfusion with at least 2 red packed cell concentrates
based on the clinical assessment by the hematologist in charge
* Hemoglobin value at least < 3 mmol/L (5 g/dl) with/without clinical symptoms
* Clinical signs of hemolysis: not-detectable haptoglobin (mandatory) and
increased lactate dehydrogenase (LDH) eventually combined with
hyperbilirubinemia (increased direct and/or indirect bilirubin), lactate.
* Age * 18 years
* Written informed consent
* Women of child bearing potential must have had a negative serum pregnancy
test 7 days prior to the start of study drug
Exclusion criteria
* History of arterial and/or venous thromboembolic events in the absence of an
actual treatment with Vitamin K-antagonists
* Concomitant use of therapeutic doses of heparin
* Female patients who are pregnant or breast feeding or adults of reproductive
potential who are not using effective birth control methods. If barrier
contraceptives are being used, these must be continued throughout the trial by
both sexes. Oral contraceptives only are not acceptable.
* Patients with known HIV seropositivity or chronic active hepatitis
* Patients who have any severe and/or uncontrolled medical condition
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2012-003710-13-NL |
| CCMO | NL41820.018.12 |
| Other | NL8164 |