Clinical trial NCT03008642: CO-Rebreathing in Comparison to Isotopic Red Cell Volume Determination in the Diagnosis of Primitive and Secondary Polycythemia
Official title: CO-Rebreathing in Comparison to Isotopic Red Cell Volume Determination in the Diagnosis of Primitive and Secondary Polycythemia: a Multicentric Study. Co-Rebreathing for the Measurement of Total Red Cell Mass in Polycythemia.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Polycythemia
Keywords: Polycythemia
CO-Rebreathing
red cell mass determination
myeloproliferative neoplasms
Lead sponsor: Centre Hospitalier Universitaire, Amiens
Sponsor class: OTHER
First posted: 2017-01-02
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The optimized CO-Rebreathing is an efficient method to evaluate the red cell mass and has been used in the vast majority of studies in sport medicine. However, this method has never been evaluated on a large scale in the diagnosis of primitive or secondary polycythemia. The standard procedure to evaluate the red cell mass is based on isotopic measurement using Cr51-labelled red cells, but its lack of availability in many centers highlights the need for a non-invasive and rapid alternative method. The purpose of this study is to evaluate and validate the CO-Rebreathing method in this set of indications.

Detailed description: The definition of a true polycythemia is stricto sensu an increased red cell mass (RCM) above 125% of the expected value depending on the size and the weight of the patient. However, this measurement requires an isotopic labeling of red cells and is not available in most of the hospitals. Therefore, the diagnosis of polycythemia, and particularly Polycythemia Vera (PV) is based on routine red blood cells parameters, i.e. hemoglobin level and hematocrit. If these parameters are efficient in marked polycythemia, discrepancies have been observed in milder cases. Two situations where a RCM evaluation is particularly required can be described:

* In patients with a hematocrit level between 52 and 60% (men) or between 48 and 56% (women) in order to limit invasive investigations to patients with a confirmed polycythemia diagnosis
* In JAK2V617F positive myeloproliferative neoplasms (MPN) with hematocrit and hemoglobin levels under the PV cut-off in order to discriminate between masked PV and essential thrombocythemia CO-Rebreathing is a fast, non invasive alternative method for RCM evaluation. It is based on the high affinity of carbon monoxide (CO) for hemoglobin. The decrease in the HbCO percentage after CO inhalation is dependent on the total hemoglobin mass from which RCM can be obtained. The investigators propose a tri-centric study evaluating CO-Rebreathing as an alternative tool to measure RCM in the diagnosis of polycythemia in the two categories of patients described above.

Eligibility criteria: Inclusion Criteria:

1. Adult patient
2. Informed consent obtained
3. Requirement of an isotopic red cell mass determination:

   a - Hematocrit between 52 and 60% (men) or 48 and 56% (women) with no argument for a PV (JAK2V617F negative, EPO level normal/high).

   b - Patients with a JAK2V617F positive MPN and a hematocrit level between 46 and 50% (women) or 48 and 52% for men.
4. No recent vascular event (\<6 mois)
5. No unstable coronaropathy
6. Non smoking since 24 hours.
7. ECOG \<2
8. Negativity of pregnancy test/effective contraception for childbearing age women,
9. Health insurance

Exclusion Criteria:

1. Recent venous event \<1 months, cerebral stroke \< 6 mois)
2. Evolutive cardiopathy (\< 6 months)
3. Chronic Respiratory failure
4. Smokers with no withdrawal in the last 24 hours before CO-Rebreathing
5. Basal HbCO\>7% the day of CO-Rebreathing
6. Pregnant or breast feeding women
7. Patient enable to give an informed consent
8. Inclusion in an interventional clinical trial in the last three months.
9. Any contraindication to lung function testing

Primary outcomes:
measure: equivalence of RCM determination by CO-Rebreathing in comparison to the traditional isotopic measurement in the diagnosis of polycythemia
timeFrame: 1 month
Secondary outcomes:
measure: AE / SAE / EI
timeFrame: 1 month
measure: Cumulative incidence of thrombotic and hemorrhagic complications
timeFrame: 1 month
measure: Deaths and causes
timeFrame: 1 month
measure: Analysis of the results of VGTCO and VGTi
timeFrame: 1 month
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens Picardie
state: Picardie
Study officials:
affiliation: CHU Amiens-Picardie
name: Loïc GARCON, professor
role: STUDY_DIRECTOR
affiliation: CHU Henri Mondor, France
name: Lydia ROY, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Universitaire Dijon
name: Marjolaine GEORGES, Doctor
role: PRINCIPAL_INVESTIGATOR
References: