Acute Chest SyndromeARCADNCT06214845
Early-goal Directed Automated Red Blood Cell Exchange for Acute Chest Syndrome in Sickle Cell Disease
A study testing Red blood cell EXchange (REX) in people with Acute Chest Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Chest Syndrome
- What is being tested?
- Red blood cell EXchange (REX)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 1 siteFrance
- Study dates
- 1 Mar 2024to 1 Sep 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Express informed consent from the relatives or the patient himself, or emergency inclusion procedure in case of inability of patient or proxy relatives to give consent NB: Patients not affiliated to social security will be included in the study given the precarious social situation of many patients with SCD
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Armand MEKONTSO DESSAP
Créteil, Val De Marne, 94010
Armand MEKONTSO DESSAP, armand.dessap@aphp.fr
About this study
Official title: Early-goal Directed Automated Red Blood Cell Exchange for Acute Chest Syndrome in Sickle Cell Disease: a Multicentre, Randomised, Clinical Trial
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
- Being tested
- Red blood cell EXchange (REX)
- Keywords
- Sickle cell disease (SCD), Acute chest syndrome (ACS), Red blood cell exchange (REX), Oxygen, Respiratory support
- Medical subject headings
- Acute Chest Syndrome, Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Red blood cell EXchange (REX)Procedure or surgery
Also called Automated REX
A single automated REX will be performed, as soon as possible after randomization.
| Study group | Role | What they receive |
|---|---|---|
| Automated REX | Experimental | Automated REX Receives: 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) Receives: Procedure: Red blood cell EXchange (REX) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 48 hours after randomization
Secondary outcomes (8)
Number of participants with complications during hospitalisation and within 3 months following randomisation
Measured: Up to 3 months
Time to discharge
Length of hospital stay
Measured: Up to 3 months
Mortality
During hospitalisation and within 28 days and 3 months following randomisation
Measured: Up to 3 months
Number of participants need for noninvasive respiratory support
high flow nasal oxygen, continuous positive airway pressure, or bilevel non-invasive ventilation)
Measured: Up to 28 days
Number of participants readmitted for VOC or ACS
Measured: Up to 3 months
Rate of haemoglobin S (HbS) after the first REX and at day-3
Measured: Up to 3 days
Number of participants with change in arterial blood gases and routine biology
routine laboratory tests including: complete blood count, arterial blood gas, serum creatinine, aspartate and alanine aminotransferase (AST/ALT), total and direct bilirubin, lactate dehydrogenase (LDH), CRP; blood electrolyte panel
Measured: 3 and 6 days after randomization
Number of participants with improved chest imaging
Measured: 3 and 6 days after randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2024
- Study start1 Mar 2024 (estimated)
- Primary completion3 Jun 2026 (estimated)
- Study completion1 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Chest SyndromeStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06214845
- Sponsor's protocol ID
- APHP230784
- Acronym
- ARCAD
- Status last verified
- Jan 2024
- First submitted
- 2 Jan 2024
- Last updated
- 22 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early-goal Directed Automated Red Blood Cell Exchange for Acute Chest Syndrome in Sickle Cell Disease: a Multicentre, Randomised, Clinical Trial
- ClinicalTrials.gov ID
- NCT06214845
- Acronym / sponsor ID
- ARCAD / APHP230784
- Conditions
- Acute Chest Syndrome
- Keywords
- Sickle cell disease (SCD), Acute chest syndrome (ACS), Red blood cell exchange (REX), Oxygen, Respiratory support
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 1 Mar 2024 (estimated)
- Primary completion
- 3 Jun 2026 (estimated)
- Study completion
- 1 Sep 2026 (estimated)
- First posted
- 22 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Automated REX | Experimental | Procedure: Red blood cell EXchange (REX)Automated REX |
| Manual REX | Active comparator | Procedure: Red blood cell EXchange (REX)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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Red blood cell EXchange (REX)Also: Automated REXA single automated REX will be performed, as soon as possible after randomization. | Procedure or surgery | Automated REX, Manual REX |
Primary outcome
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 frame: 48 hours after randomization
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.
8 secondary outcomes
Number of participants with complications during hospitalisation and within 3 months following randomisation
Time frame: Up to 3 months
Time to discharge
Time frame: Up to 3 months
Mortality
Time frame: Up to 3 months
Number of participants need for noninvasive respiratory support
Time frame: Up to 28 days
Number of participants readmitted for VOC or ACS
Time frame: Up to 3 months
Rate of haemoglobin S (HbS) after the first REX and at day-3
Time frame: Up to 3 days
Number of participants with change in arterial blood gases and routine biology
Time frame: 3 and 6 days after randomization
Number of participants with improved chest imaging
Time frame: 3 and 6 days after randomisation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2024.
- Individual participant dataSharing planned: No. DATAS ARE OWN BY ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS, PLEASE CONTACT SPONSOR FOR FURTHER INFORMATION
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Red blood cell EXchange (REX) in people with Acute Chest Syndrome, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Armand MEKONTSO DESSAP (+33 1 45 17 85 11, armand.dessap@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 frame: 48 hours after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2024.