Algorithm for Apherisis Monitoring and Prescription Assistance in Sickle Cell Patients (ALGODREP)

Sickle Cell Disease Clinical Trial

— ALGODREP  

Official title:

Validation d'Une Stratégie de Programme Transfusionnel Par Erythraphérèse basée Sur un Algorithme d'Aide à la Prescription Transfusionnelle Chez Les Patients Adultes Drépanocytaires

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04076683
• Other study ID #: 2016-A01411-50
• Status: Completed
• Phase: N/A
• Start date: January 5, 2022
• Est. completion date: November 30, 2023

Study information

• Verified date: January 2024
• Source: Etablissement Français du Sang
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objective of this study is to prove the superiority of a procedure which calculates the volume of RBCs to transfuse and the time between apheresis based on this algorithm, compared to the current procedure. The primary endpoint would be the number of patients with individually achieved objectives in terms of % HbS before each apheresis (which reflects the effectiveness of the previous apheresis) over a period of 12 months. The secondary objectives would be to compare the volume differences of transfused RBCs in both groups over a period of 12 months, the occurrence of clinical events and the satisfaction of patients and physicians.

The investigators hope that this study would improve the efficiency and the performance of apheresis in sickle cell patients. The investigators also hope to facilitate the organization of procedures with the flexibility that would allow the use of this algorithm.

Description:

Sickle cell disease (SCD) is the most common genetic disease leading to abnormal hemoglobin (HbS). Chronic complications can be severe and affect multiple organs. Among them, cerebrovascular disease is one of the most serious leading to a high risk of stroke. These complications often require blood exchange transfusions (BET) in order to replace red blood cells (RBC) containing HbS (from patients) by GR containing HbA (blood donors), and thereby stop the harmful pathophysiological cascade. The indications of long-term apheresis are mostly, but not exclusively, represented by cerebral vasculopathy (85% in our center), and chronic organ damages. Long-term BET in cerebral vasculopathy may considerably reduce the risk of stroke while stopping them leads to a recurrence of this risk, hence there is a need to do them regularly (on average every 4 to 6 weeks) with an objective of HbS ≤ 30%. This objective may be less stringent in the case of other indications.

Two methods are used: a manual method which is feasible anywhere and the apheresis which is preferred because of its better efficacy in achieving the targets of HbS percentage. It also limits transfusion hemochromatosis.

The volume required for BET by apheresis as well as the optimal period between apheresis sessions are empirically determined.

In our practice, the investigators noticed that this method did not allow to steadily obtaining the %HbS objective and the interval between apheresis was variable, in part conditioned by the availability of machines. This implies a real risk of occurrence of recurrent stroke in patients with cerebral vascular disease and may cause a lack of flexibility in the timing of appointments.

Thereby the principal investigator and the biostatistician created an algorithm to compute the volume of blood to be transfused and the interval between apheresis which are necessary to maintain an individual objective of HbS percentage. This algorithm has been obtained by statistical analysis of apheresis performed at Henri Mondor Hospital over a period of 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: November 30, 2023
• Est. primary completion date: November 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18 years or older

• Have sickle cell disease, defined as those individuals with HbSS or HbSß0Thal

• Included in a Blood Exchange Transfusion program (apherisis)

• Benefiting from social insurance

• Accepting to participate in the study and having signed the informed consent

Exclusion Criteria:

• Have sickle cell disease defined with S-ß+thal

• Receiving EPO treatment

• Pregnant or breast-feeding women

• Lack of effective contraception in women in childbearing age

• Patient under guardianship

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Device:
• Algodrep
Algorithm computing the volume of blood to be transfused and the interval between apheresis which are necessary to maintain an individual objective of HbS percentage.

Locations

Country	Name	City	State
France	Centre de Santé EFS	Besançon	Bourgogne Franche-Comté
France	Centre de Santé EFS	Bordeaux	Nouvelle-Aquitaine
France	Hôpital Henri Mondor	Créteil	Ile-de-France
France	CHU Kremlin Bicêtre	Le Kremlin-Bicêtre	Ile De France
France	Centre de Santé EFS	Rennes	Bretagne
France	EFS Rhône-Alpes-Auvergne	Saint-Priest-en-Jarez	Auvergne Rhône-Alpes
France	Centre de Santé EFS	Tours	Centre-Val De Loire
Martinique	CHU de Martinique	Le Lamentin

Sponsors (3)

Lead Sponsor	Collaborator
Etablissement Français du Sang	Assistance Publique - Hôpitaux de Paris, Université Paris Est Créteil

Countries where clinical trial is conducted

France,  Martinique, 

References & Publications (15)

Abboud MR, Yim E, Musallam KM, Adams RJ; STOP II Study Investigators. Discontinuing prophylactic transfusions increases the risk of silent brain infarction in children with sickle cell disease: data from STOP II. Blood. 2011 Jul 28;118(4):894-8. doi: 10.1182/blood-2010-12-326298. Epub 2011 Jun 1. — View Citation

Adams RJ, Brambilla D; Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) Trial Investigators. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N Engl J Med. 2005 Dec 29;353(26):2769-78. doi: 10.1056/NEJMoa050460. — View Citation

Adams RJ, McKie VC, Hsu L, Files B, Vichinsky E, Pegelow C, Abboud M, Gallagher D, Kutlar A, Nichols FT, Bonds DR, Brambilla D. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med. 1998 Jul 2;339(1):5-11. doi: 10.1056/NEJM199807023390102. — View Citation

Belcher JD, Chen C, Nguyen J, Milbauer L, Abdulla F, Alayash AI, Smith A, Nath KA, Hebbel RP, Vercellotti GM. Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease. Blood. 2014 Jan 16;123(3):377-90. doi: 10.1182/blood-2013-04-495887. Epub 2013 Nov 25. — View Citation

Eltzschig HK, Carmeliet P. Hypoxia and inflammation. N Engl J Med. 2011 Feb 17;364(7):656-65. doi: 10.1056/NEJMra0910283. No abstract available. — View Citation

Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011 Nov 7;17(11):1391-401. doi: 10.1038/nm.2507. — View Citation

Gueguen A, Mahevas M, Nzouakou R, Hosseini H, Habibi A, Bachir D, Brugiere P, Lionnet F, Ribei JA, Godeau B, Girot R, Ibrahima V, Calvet D, Galacteros F, Bartolucci P. Sickle-cell disease stroke throughout life: a retrospective study in an adult referral center. Am J Hematol. 2014 Mar;89(3):267-72. doi: 10.1002/ajh.23625. — View Citation

Lionnet F, Arlet JB, Bartolucci P, Habibi A, Ribeil JA, Stankovic K; groupe de recommandations et d'etude de la drepanocytose de l'adulte (GREDA). [Guidelines for management of adult sickle cell disease]. Rev Med Interne. 2009 Sep;30 Suppl 3:S162-223. doi: 10.1016/j.revmed.2009.07.001. Epub 2009 Aug 26. French. — View Citation

Nahavandi M, Nichols JP, Hassan M, Gandjbakhche A, Kato GJ. Near-infrared spectra absorbance of blood from sickle cell patients and normal individuals. Hematology. 2009 Feb;14(1):46-8. doi: 10.1179/102453309X385133. — View Citation

Nahavandi M, Tavakkoli F, Hasan SP, Wyche MQ, Castro O. Cerebral oximetry in patients with sickle cell disease. Eur J Clin Invest. 2004 Feb;34(2):143-8. doi: 10.1111/j.1365-2362.2004.01307.x. — View Citation

Quinn CT, Ahmad N. Clinical correlates of steady-state oxyhaemoglobin desaturation in children who have sickle cell disease. Br J Haematol. 2005 Oct;131(1):129-34. doi: 10.1111/j.1365-2141.2005.05738.x. — View Citation

Quinn CT, Sargent JW. Daytime steady-state haemoglobin desaturation is a risk factor for overt stroke in children with sickle cell anaemia. Br J Haematol. 2008 Feb;140(3):336-9. doi: 10.1111/j.1365-2141.2007.06927.x. Epub 2007 Nov 27. — View Citation

Setty BN, Stuart MJ, Dampier C, Brodecki D, Allen JL. Hypoxaemia in sickle cell disease: biomarker modulation and relevance to pathophysiology. Lancet. 2003 Nov 1;362(9394):1450-5. doi: 10.1016/S0140-6736(03)14689-2. — View Citation

Waltz X, Pichon A, Lemonne N, Mougenel D, Lalanne-Mistrih ML, Lamarre Y, Tarer V, Tressieres B, Etienne-Julan M, Hardy-Dessources MD, Hue O, Connes P. Normal muscle oxygen consumption and fatigability in sickle cell patients despite reduced microvascular oxygenation and hemorheological abnormalities. PLoS One. 2012;7(12):e52471. doi: 10.1371/journal.pone.0052471. Epub 2012 Dec 20. — View Citation

Waltz X, Pichon A, Mougenel D, Lemonne N, Lalanne-Mistrih ML, Sinnapah S, Tarer V, Tressieres B, Lamarre Y, Etienne-Julan M, Hue O, Hardy-Dessources MD, Connes P. Hemorheological alterations, decreased cerebral microvascular oxygenation and cerebral vasomotion compensation in sickle cell patients. Am J Hematol. 2012 Dec;87(12):1070-3. doi: 10.1002/ajh.23318. Epub 2012 Aug 22. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with individually achieved objectives in terms of % HbS		For each apherisis over a 12 months period
Secondary	Volume of transfused RBCs		For each apherisis over a 12 months period
Secondary	Number of transfused RBCs		For each apherisis over a 12 months period
Secondary	Number of apherisis per participant		Over a 12 months period
Secondary	Hematocrit (percentage)		For each apherisis over a 12 months period
Secondary	Hemoglobin (g/dL)		For each apherisis over a 12 months period
Secondary	Number of reticulocyte (g/L),		For each apherisis over a 12 months period
Secondary	Percentage of reticulocyte		For each apherisis over a 12 months period
Secondary	Lactate dehydrogenase (UI/L)		For each apherisis over a 12 months period
Secondary	Creatinine (mg/L)		For each apherisis over a 12 months period
Secondary	Alanine aminotransferase (UI/L)		For each apherisis over a 12 months period
Secondary	Aspartate aminotransferase (UI/L)		For each apherisis over a 12 months period
Secondary	Bilirubin T (mg/dL)		For each apherisis over a 12 months period
Secondary	Percentage of alloimmunisation events evaluated with irregular red cell antibodies measure		For each apherisis over a 12 months period
Secondary	Quality of life questionnaire (SF-36)		At baseline and in 12 months
Secondary	Physician satisfaction survey for each participant		Month 12