Early-goal Directed Automated Red Blood Cell Exchange for Acute Chest Syndrome in Sickle Cell Disease

NCT06214845 | Not Yet Recruiting

• 1 other identifier: APHP230784
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

Sickle cell disease (SCD) is characterized by recurrent vaso-occlusive pain crisis (VOC), which may evolve to acute chest syndrome (ACS), the most common cause of death among adult patients with SCD. Currently, there is no etiologic treatment to abort ACS. Therefore, management of ACS mostly involve a symptomatic approach including in routine, and as per recommendations, hydration, analgesics, supplemental oxygen, and transfusion. The polymerisation of sickle haemoglobin (HbS) is one major feature in the pathogenesis of vaso-occlusion. Current guidelines recommend red blood cell exchange transfusion (REX) in patients with severe ACS in order to improve oxygenation and reduce HbS concentration to blunt sickling. REX is often preferred over simple transfusion in this setting because it rapidly reduces HbS without raising final haematocrit. There are currently two methods for REX: manual (with sequential phlebotomies and transfusions) or automated (erythrocytapheresis). The former allows a sober use of red blood cell packs, while the latter achieves haematological targets (HbS and haematocrit) quickly and more consistently, but requires a special equipment and trained staff. As a result of inflammation and intravascular hemolysis, the plasma of patients with ACS may also contain several components that promote vaso-occlusion, lung injury and organ failure, including cytokines (e.g., IL-6), free haemoglobin and free haem. Conversely, it is depleted in haptoglobin and hemopexin, which normally bind to and clear cell-free haemoglobin. The addition of therapeutic plasma exchange to erythrocytapheresis during automated REX may therefore have a dual beneficial effect in patients with overt intravascular hemolysis: i) deplete the inflammatory mediators and products of hemolysis; ii) replete haptoglobin and hemopexin. REX modalities (automated vs manual) have not been tested during ACS. The hypothesis is that early-goal directed automated REX may accelerate the resolution of severe ACS as compared to manual REX.

Conditions

Acute Chest Syndrome

Keywords

Sickle cell disease (SCD); Acute chest syndrome (ACS); Red blood cell exchange (REX); Oxygen; Respiratory support

Outcome Measures

Primary Outcomes (1)

• efficacy of automated (vs manual) REX to reduce time to successful weaning from both supplemental oxygen and any respiratory support (non-invasive or invasive) in adult SCD patients with hypoxemic ACS.

  Time to successful weaning from both supplemental oxygen and any respiratory support, defined as SpO2 ≥ 95% without oxygen and any respiratory support (non-invasive or invasive) during 48 hours.

  48 hours after randomization

Secondary Outcomes (8)

• Number of participants with complications during hospitalisation and within 3 months following randomisation

  Up to 3 months

• Time to discharge

  Up to 3 months

• Mortality

  Up to 3 months

• Number of participants need for noninvasive respiratory support

  Up to 28 days

• Number of participants readmitted for VOC or ACS

  Up to 3 months

Study Arms (2)

Automated REX

EXPERIMENTAL

Automated REX

Procedure: Red blood cell EXchange (REX)

Manual REX

ACTIVE COMPARATOR

First manual REX will be performed as soon as possible after randomisation, and the patient will be re-assessed every 24 hours (repeated manual REX will be allowed in case of clinical worsening after 24 or 48 hours or in the absence of clinical improvement after 72 hours)

Procedure: Red blood cell EXchange (REX)

Interventions

Red blood cell EXchange (REX) PROCEDURE

A single automated REX will be performed, as soon as possible after randomization.

Also known as: Automated REX

Automated REX; Manual REX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Patient with major sickle cell disease syndrome (SS, SC, Sβ0 or Sβ+)
• ACS, as defined by the association of fever and/or acute respiratory symptoms with a new pulmonary infiltrate on chest imaging
• Requiring supplemental oxygen ≥ 2 L/min for SpO2 ≥ 95%
• With an indication for REX given the hypoxemic ACS, as per recommendations

You may not qualify if:

• Patient having both ACS criteria and need for supplemental oxygen ≥ 2 L/min for SpO2 ≥ 95% since more than 72 hours
• Red blood cell transfusion or REX during the current ACS episode
• Any past medical history of delayed haemolytic transfusion reaction
• History of \< 12 transfused RBC or anti-red blood cell antibody production on the one hand and no possibility for matching on Rh/K, antibody specificity, and extended to Duffy (Fya), Kidd (Jka and Jkb) and MNS (M, N, S and s) phenotypes on the other hand (12)
• Known legal incapacity (guardianship, curatorship)
• Prisoners or subjects who are involuntarily incarcerated
• Anatomical factors precluding placement of an adequate venous access
• Known pregnancy or current lactation

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Armand MEKONTSO DESSAP

Créteil, Val De Marne, 94010, France

Location

MeSH Terms

Conditions

Acute Chest Syndrome; Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Armand MEKONTSO DESSAP

CONTACT

+33 1 45 17 85 11; armand.dessap@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A multicentre, randomised, controlled, superiority clinical trial. Participants will be randomly assigned to one of the two groups of the study (manual or automated REX) with a 1:1 allocation as per a computer generated randomisation list stratified by site and type of respiratory support as follows: low flow-oxygen vs noninvasive respiratory support (i.e., high low oxygen or continuous positive airway pressure or noninvasive ventilation) vs invasive ventilation.

Study Record Dates

• First Submitted: January 2, 2024
• First Posted: January 22, 2024
• Study Start: March 1, 2024
• Primary Completion (Estimated): June 3, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: January 22, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)