Sickle Cell DiseasePHEDREANCT07246265
Morphine Clearance and Glomerular Filtration in Sickle Cell Patients in Crisis in Intensive Care
A study testing Injection of iohexol for glomerular filtration rate (GFR) measurement in people with Sickle Cell Disease and Glomerular Hyperfiltration, run by University Hospital, Tours at 6 sites in France.
Trial summary
Background: Sickle cell disease is a genetic disorder of haemoglobin (which carries oxygen in red blood cells). The shape of sickle cell-patients' red blood cells is abnormal. Thus, red blood cells can be blocked in small vessels, responsible for painful crises due to a lack of downstream circulation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sickle Cell Disease, Glomerular Hyperfiltration, Sickle Cell Nephropathy
- What is being tested?
- Injection of iohexol for glomerular filtration rate (GFR) measurement
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 6 sitesFrance
- Study dates
- 5 Mar 2026to Sep 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Patient ≥ 18 years old
- Known homozygous sickle cell disease SS, SC, S-beta+, or S-beta0
- Admitted in an intensive care unit
- Clinical diagnosis of vaso-occlusive crisis and/or acute chest syndrome
- Receiving PCA treatment with morphine
- Patient's consent for study participation and/or from a relative if case of patient's incapacity
- Affiliation to social protection
Who cannot join
- Patient previously included in the study during a previous stay
- Injection of iodinated contrast medium outside the scope of the study within 24 hours prior to inclusion, or scheduled within 9 hours following the scheduled time of iohexol injection
- Contraindication to iohexol: known or suspected immediate or delayed hypersensitivity, thyrotoxicosis.
- Patient undergoing morphine treatment or substitution treatment such as methadone or buprenorphine prior to hospitalization (having received morphine or a derivative regardless of the route of administration in the week prior to hospitalization).
- Chronic liver disease likely to interfere with morphine metabolism (cirrhosis )
- Any condition that contraindicates the use of morphine according to the summary of product characteristics
Show all 9Show fewer
- Patients under legal protection
- Pregnant or breastfeeding women
- Need for extrarenal epuration within 24 hours of inclusion
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Charlotte SALMON-GANDONNIERE, MD contact
6 sites in 1 country
France6 sites, 6 recruiting
- Not yet recruiting
Henri-Mondor
Créteil
Armand MEKONTSO DESSAP, +33 1 45 17 85 11, armand.dessap@aphp.fr
Armand MEKONTSO DESSAP
- Not yet recruiting
CH Le Mans
Le Mans, 72000
Mickael LANDAIS, +332 44 71 07 43, mlandais@ch-lemans.fr
Mickael LANDAIS
- Not yet recruiting
CHU de Nantes
Nantes, 44093
Maité Lacou AGBAKOU, +332 40 08 73 69, maite.lacouagbakou@chu-nantes.fr
Maité Lacou AGBAKOU
- Not yet recruiting
CHU d'Orléans
Orléans, 45067
Grégoire MULLER, +332 38 22 95 34, gregoire.muller@chr-orleans.fr
Grégoire MULLER
- Not yet recruiting
CHU de Rennes
Rennes
Benoit PAINVIN, +332 99 28 42 48, benoit.painvin@chu-rennes.fr
Benoit PAINVIN
- Recruiting
CHRU de Tours
Tours, France, 37044
Charlotte SALMON GANDONNIERE, +33 2 47 47 39 09, charlotte.salmon.gandonniere@gmail.com
cpcq@chu-tours.fr
About this study
Background: Sickle cell disease is a genetic disorder of haemoglobin (which carries oxygen in red blood cells). The shape of sickle cell-patients' red blood cells is abnormal. Thus, red blood cells can be blocked in small vessels, responsible for painful crises due to a lack of downstream circulation. These crisis (acute vaso-occlusive crisis) require strong treatment based on morphine, and often require intensive care.However, treatment is often insufficiently effective. Patient can also experiment acute chest syndrome, a complication of vaso-occlusive crisis, which can be responsible for respiratory failure. In addition, patients with sickle cell disease frequently have kidney damage called sickle cell nephropathy, which in the early stages of the disease is responsible for renal hyperfiltration, meaning that the kidneys filter the blood more than necessary, with faster elimination of drugs. For example, it is known that higher doses of antibiotics must be used in these patients than in the general population for the same effectiveness. The hypothesis of the study is that morphine, a drug eliminated by kidneys, is underdosed in patients with sickle cell disease, which is responsible for the difficulties in achieving sufficient analgesia.
Objective: To determine the glomerular filtration rate threshold for which it is necessary to prescribe higher doses of morphine in sickle cell patients with vaso-occlusive crisis.
Read more
Methods: inclusion of 100 patients admitted to intensive care for an acute vaso-occlusive crisis or acute chest syndrome and receiving morphine. Within 24 hours of study inclusion, four morphine dosages will be performed, in parallel with a precise determination of the glomerular filtration rate by measuring the elimination rate of a tracer, 100% eliminated by the kidneys and injected at the start of the study. This tracer is iohexol, a contrast agent commonly used in radiology. Morphine underdosage will be interpretated regarding glomerular filtration rate. The effectiveness of analgesia and the amount of analgesics required will be also be analyzed.
Outlook: At the end of this study, the investigators will be able to offer adapted doses of morphine for sickle cell patients in crisis, adapted to glomerular filtration rate, in the aim of personalizing analgesia.
- Conditions
- Sickle Cell Disease, Glomerular Hyperfiltration, Sickle Cell Nephropathy, Vaso-Occlusive Crises, Acute Chest Syndrome
- Being tested
- Injection of iohexol for glomerular filtration rate (GFR) measurement
- Medical subject headings
- Anemia, Sickle Cell, Vaso-Occlusive Crises, Acute Chest Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Injection of iohexol for glomerular filtration rate (GFR) measurementDrug
All patients will receive the same intervention. In included patients, 5 mL of iohexol will be injected, followed by blood sampling 5min, 1hr and 9hrs after iohexol injection for GFR measurement (as iohexol is known to be an exogenous maker for GFR measurement).
Analgesia will be protocolized, based in particular on self-administered morphine (patient-controlled-analgesia). Morphine clearance will be measured thanks to 4 blood samples. Blood sampling for morphine and iohexol dosages will be synchronized in order to reduce the number of vascular punctures. Moreover, the first blood sample (5 minutes after iohexol injection) and the 4th blood sample for morphine dosage will be performed at the time of the daily biological analysis, still in order to reduce the number of vascular punctures. Thus, iohexol will be injected 5 minutes before the daily blood sampling for routine biological analysis.
| Study group | Role | What they receive |
|---|---|---|
| Determination of glomerular filtration rate by Iohexol | Experimental | Four morphine dosages, and a precise determination of the glomerular filtration rate by the measure of the elimination rate of iohexol will be carried out. The investigators will analyse in which patients and for which glomerular filtration rate there is morphine underdosage and simultaneously evaluate the effectiveness of analgesia and the amount of analgesics required. Receives: Drug: Injection of iohexol for glomerular filtration rate (GFR) measurement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Therapeutic failure
Prediction of therapeutic failure based on glomerular filtration rate according to the CKD-EPI formula (area under roc curve). Therapeutic failure is defined as a percentage of relief assessed by the verbal numerical scale not reaching 30% within 24 hours.
Measured: 24 hours
Glomerular filtration rate according to the CKD-EPI formula
Glomerular filtration rate according to the CKD-EPI formula
Measured: 5 minutes
Secondary outcomes (10)
Clearance of morphine and its metabolites M3G and M6G
Correlation between clearance of morphine (and its metabolites M3G and M6G) and glomerular filtration rate according to the CKD-EPI formula.
Measured: 24 hours
Morphine dose administered
Total dose of morphine administered during the day
Measured: 24 hours
Morphine dose administred
Total dose of morphine administered each day
Measured: Day 7
Pain progression using the Visual Analog Scale
Pain intensity will be assessed using the Visual Analog Scale (VAS), a 100-mm horizontal line ranging from 0 mm (no pain) to 100 mm (worst imaginable pain). Participants will indicate their pain level by marking a point on the line. Higher scores represent more severe pain. The change from baseline will be measured to assess pain progression.
Measured: Every 4 hours for the first 7 days
Pain progression using a Numeric Rating Scale
Pain intensity will be assessed using the Numeric Rating Scale (NRS), which ranges from 0 (no pain) to 10 (worst imaginable pain). Participants verbally rate their pain on this numeric scale. Higher scores indicate worse pain.
Measured: Every 4 hours for the first 7 days
Patient Global Impression of Change (PGIC) Over the First 7 Days
The Patient Global Impression of Change (PGIC) scale is a patient-reported outcome measure that assesses the patient's perception of change in their overall health status since the beginning of treatment. It is a 7-point Likert scale ranging from 1 (very much improved) to 7 (very much worse). Lower scores indicate a better outcome (improvement), while higher scores indicate worsening condition. PGIC will be assessed daily every 24 hours during the first 7 days of treatment.
Measured: Daily, every 24 hours, from Day 1 to Day 7
Number of patients receiving paracetamol, nefopam, ketamine, NSAIDs, or nitrous oxide (MEOPA) within 24 hours
The therapeutic regimen will be recorded by counting the number of patients who receive each of the following analgesics within the first 24 hours: paracetamol, nefopam, ketamine, non-steroidal anti-inflammatory drugs (NSAIDs), and nitrous oxide (MEOPA).
Measured: 24 hours
Adverse effects of morphine
Adverse effects of morphine include impaired alertness, bradypnea, hypercapnia, pruritus, constipation, bloating, nausea, vomiting, and acute urinary retention.
Measured: Day 7
Glomerular filtration rate according to the CKD-EPI formula
Basal glomerular filtration rate according to the CKD-EPI formula and crisis glomerular filtration rate according to the CKD-EPI formula (5 minutes)
Measured: 5 minutes
Plasma clearance of iohexol
Sample collection for iohexol dosage
Measured: 5 minutes, 1 hour et 9 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2025
- Study start5 Mar 2026
- Primary completionSep 2028 (estimated)
- Study completionSep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07246265
- Sponsor's protocol ID
- DR230314
- Other IDs
- 2024-511985-34-00
- Acronym
- PHEDREA
- Status last verified
- Mar 2026
- First submitted
- 29 Aug 2025
- Last updated
- 10 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Morphine Clearance and Glomerular Filtration in Sickle Cell Patients in Crisis in Intensive Care
- ClinicalTrials.gov ID
- NCT07246265
- Acronym / sponsor ID
- PHEDREA / DR230314
- Conditions
- Sickle Cell Disease, Glomerular Hyperfiltration, Sickle Cell Nephropathy, Vaso-Occlusive Crises, Acute Chest Syndrome
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Study start
- 5 Mar 2026 (actual)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Sep 2028 (estimated)
- First posted
- 24 Nov 2025 (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.
Background: Sickle cell disease is a genetic disorder of haemoglobin (which carries oxygen in red blood cells). The shape of sickle cell-patients' red blood cells is abnormal. Thus, red blood cells can be blocked in small vessels, responsible for painful crises due to a lack of downstream circulation. These crisis (acute vaso-occlusive crisis) require strong treatment based on morphine, and often require intensive care.However, treatment is often insufficiently effective. Patient can also experiment acute chest syndrome, a complication of vaso-occlusive crisis, which can be responsible for respiratory failure. In addition, patients with sickle cell disease frequently have kidney damage called sickle cell nephropathy, which in the early stages of the disease is responsible for renal hyperfiltration, meaning that the kidneys filter the blood more than necessary, with faster elimination of drugs. For example, it is known that higher doses of antibiotics must be used in these patients than in the general population for the same effectiveness. The hypothesis of the study is that morphine, a drug eliminated by kidneys, is underdosed in patients with sickle cell disease, which is responsible for the difficulties in achieving sufficient analgesia.
Objective: To determine the glomerular filtration rate threshold for which it is necessary to prescribe higher doses of morphine in sickle cell patients with vaso-occlusive crisis.
Methods: inclusion of 100 patients admitted to intensive care for an acute vaso-occlusive crisis or acute chest syndrome and receiving morphine. Within 24 hours of study inclusion, four morphine dosages will be performed, in parallel with a precise determination of the glomerular filtration rate by measuring the elimination rate of a tracer, 100% eliminated by the kidneys and injected at the start of the study. This tracer is iohexol, a contrast agent commonly used in radiology. Morphine underdosage will be interpretated regarding glomerular filtration rate. The effectiveness of analgesia and the amount of analgesics required will be also be analyzed.
Outlook: At the end of this study, the investigators will be able to offer adapted doses of morphine for sickle cell patients in crisis, adapted to glomerular filtration rate, in the aim of personalizing analgesia.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Determination of glomerular filtration rate by Iohexol | Experimental | Drug: Injection of iohexol for glomerular filtration rate (GFR) measurementFour morphine dosages, and a precise determination of the glomerular filtration rate by the measure of the elimination rate of iohexol will be carried out. The investigators will analyse in which patients and for which glomerular filtration rate there is morphine underdosage and simultaneously evaluate the effectiveness of analgesia and the amount of analgesics required. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patient ≥ 18 years old
- Known homozygous sickle cell disease SS, SC, S-beta+, or S-beta0
- Admitted in an intensive care unit
- Clinical diagnosis of vaso-occlusive crisis and/or acute chest syndrome
- Receiving PCA treatment with morphine
Key exclusion criteria (9 listed)
- Patient previously included in the study during a previous stay
- Injection of iodinated contrast medium outside the scope of the study within 24 hours prior to inclusion, or scheduled within 9 hours following the scheduled time of iohexol injection
- Contraindication to iohexol: known or suspected immediate or delayed hypersensitivity, thyrotoxicosis.
- Patient undergoing morphine treatment or substitution treatment such as methadone or buprenorphine prior to hospitalization (having received morphine or a derivative regardless of the route of administration in the week prior to hospitalization).
- Chronic liver disease likely to interfere with morphine metabolism (cirrhosis )
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 |
|---|---|---|
| Injection of iohexol for glomerular filtration rate (GFR) measurementAll patients will receive the same intervention. In included patients, 5 mL of iohexol will be injected, followed by blood sampling 5min, 1hr and 9hrs after iohexol injection for GFR measurement (as iohexol is known to be an exogenous maker for GFR measurement). Analgesia will be protocolized, based in particular on self-administered morphine (patient-controlled-analgesia). Morphine clearance will be measured thanks to 4 blood samples. Blood sampling for morphine and iohexol dosages will be synchronized in order to reduce the number of vascular punctures. Moreover, the first blood sample (5 minutes after iohexol injection) and the 4th blood sample for morphine dosage will be performed at the time of the daily biological analysis, still in order to reduce the number of vascular punctures. Thus, iohexol will be injected 5 minutes before the daily blood sampling for routine biological analysis. | Drug | Determination of glomerular filtration rate by Iohexol |
Primary outcome
Therapeutic failure
Time frame: 24 hours
Prediction of therapeutic failure based on glomerular filtration rate according to the CKD-EPI formula (area under roc curve). Therapeutic failure is defined as a percentage of relief assessed by the verbal numerical scale not reaching 30% within 24 hours.
Glomerular filtration rate according to the CKD-EPI formula
Time frame: 5 minutes
Glomerular filtration rate according to the CKD-EPI formula
10 secondary outcomes
Clearance of morphine and its metabolites M3G and M6G
Time frame: 24 hours
Morphine dose administered
Time frame: 24 hours
Morphine dose administred
Time frame: Day 7
Pain progression using the Visual Analog Scale
Time frame: Every 4 hours for the first 7 days
Pain progression using a Numeric Rating Scale
Time frame: Every 4 hours for the first 7 days
Patient Global Impression of Change (PGIC) Over the First 7 Days
Time frame: Daily, every 24 hours, from Day 1 to Day 7
Number of patients receiving paracetamol, nefopam, ketamine, NSAIDs, or nitrous oxide (MEOPA) within 24 hours
Time frame: 24 hours
Adverse effects of morphine
Time frame: Day 7
Glomerular filtration rate according to the CKD-EPI formula
Time frame: 5 minutes
Plasma clearance of iohexol
Time frame: 5 minutes, 1 hour et 9 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2026.
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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.
Charlotte SALMON-GANDONNIERE, MD contact
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Injection of iohexol for glomerular filtration rate (GFR) measurement in people with Sickle Cell Disease and Glomerular Hyperfiltration, run by University Hospital, Tours at 6 sites 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 7 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 10 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Charlotte SALMON-GANDONNIERE, MD (+33 2 47 47 38 55 ext. poste 7 12 14, charlotte.salmon.gandonniere@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Therapeutic failure (time frame: 24 hours). The study lists 2 primary outcomes in all. 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 10 Mar 2026.