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

• ClinicalTrials.gov Identifier: NCT04076683
• Recruitment Status: Unknown
• First Posted: September 3, 2019
• Last Update Posted: September 3, 2019
• Sponsor: Etablissement Français du Sang
• Collaborators: Assistance Publique - Hôpitaux de Paris; Université Paris Est Créteil
• Information provided by (Responsible Party): Etablissement Français du Sang

Tracking Information

• First Submitted Date: August 26, 2019
• First Posted Date: September 3, 2019
• Last Update Posted Date: September 3, 2019
• Estimated Study Start Date: November 2019
• Estimated Primary Completion Date: November 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 30, 2019): Number of patients with individually achieved objectives in terms of % HbS [ Time Frame: For each apherisis over a 12 months period ]
• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: August 30, 2019)

• Volume of transfused RBCs [ Time Frame: For each apherisis over a 12 months period ]
• Number of transfused RBCs [ Time Frame: For each apherisis over a 12 months period ]
• Number of apherisis per participant [ Time Frame: Over a 12 months period ]
• Hematocrit (percentage) [ Time Frame: For each apherisis over a 12 months period ]
• Hemoglobin (g/dL) [ Time Frame: For each apherisis over a 12 months period ]
• Number of reticulocyte (g/L), [ Time Frame: For each apherisis over a 12 months period ]
• Percentage of reticulocyte [ Time Frame: For each apherisis over a 12 months period ]
• Lactate dehydrogenase (UI/L) [ Time Frame: For each apherisis over a 12 months period ]
• Creatinine (mg/L) [ Time Frame: For each apherisis over a 12 months period ]
• Alanine aminotransferase (UI/L) [ Time Frame: For each apherisis over a 12 months period ]
• Aspartate aminotransferase (UI/L) [ Time Frame: For each apherisis over a 12 months period ]
• Bilirubin T (mg/dL) [ Time Frame: For each apherisis over a 12 months period ]
• Percentage of alloimmunisation events evaluated with irregular red cell antibodies measure [ Time Frame: For each apherisis over a 12 months period ]
• Quality of life questionnaire (SF-36) [ Time Frame: At baseline and in 12 months ]
• Physician satisfaction survey for each participant [ Time Frame: Month 12 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Algorithm for Apherisis Monitoring and Prescription Assistance in Sickle Cell Patients (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

Brief 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.

Detailed 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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Supportive Care
• Condition: 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.

Study Arms

• Experimental: Algorithm (arm A)
  Frequency and volume for apherisis proposed by algorithm and validated by the physician
  Intervention: Device: Algodrep
• No Intervention: Usual care (arm C)
  Frequency and volume for apherisis only decided by the physician (usual care)

Publications *

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 30, 2019): 65
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2021
• Estimated Primary Completion Date: November 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Age 18 years or older
• Have sickle cell disease, defined as those individuals with HbSS or HbSβ0Thal
• 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-β+thal
• Receiving EPO treatment
• Pregnant or breast-feeding women
• Lack of effective contraception in women in childbearing age
• Patient under guardianship

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Martinique

Administrative Information

• NCT Number: NCT04076683
• Other Study ID Numbers: 2016-A01411-50
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Etablissement Français du Sang
• Original Responsible Party: Same as current
• Current Study Sponsor: Etablissement Français du Sang
• Original Study Sponsor: Same as current

Collaborators

• Assistance Publique - Hôpitaux de Paris
• Université Paris Est Créteil

Investigators

• Principal Investigator: Pablo BARTOLUCCI; Henri Mondor University Hospital

• PRS Account: Etablissement Français du Sang
• Verification Date: August 2019