CO-Rebreathing in Comparison to Isotopic Red Cell Volume Determination in the Diagnosis of Primitive and Secondary Polycythemia (Poly-CO)

• ClinicalTrials.gov Identifier: NCT03008642
• Recruitment Status: Unknown
• First Posted: January 2, 2017
• Last Update Posted: February 4, 2019
• Sponsor: Centre Hospitalier Universitaire, Amiens
• Information provided by (Responsible Party): Centre Hospitalier Universitaire, Amiens

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Polycythemia	Other: CO-Rebreathing technique at diagnosis of polycythemia	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• 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.
• Estimated Study Start Date: April 1, 2019
• Estimated Primary Completion Date: May 1, 2020
• Estimated Study Completion Date: May 1, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: CO-Rebreathing; The intervention consists in one red cell mass determination using the CO-Rebreathing technique at diagnosis of polycythemia, in addition to the regular tests performed in this indication, including RCM isotopic measurement.	Other: CO-Rebreathing technique at diagnosis of polycythemia; The intervention consists in one red cell mass determination using the CO-Rebreathing technique at diagnosis of polycythemia, in addition to the regular tests performed in this indication, including RCM isotopic measurement.

Outcome Measures

Primary Outcome Measures :

1. equivalence of RCM determination by CO-Rebreathing in comparison to the traditional isotopic measurement in the diagnosis of polycythemia [ Time Frame: 1 month ]
   The primary outcome is to prove the equivalence of RCM determination by CO-Rebreathing in comparison to the traditional isotopic measurement in the diagnosis of polycythemia.

Secondary Outcome Measures :

1. AE / SAE / EI [ Time Frame: 1 month ]
   Incidence, grade type according to NCI-CTCAE v4.0
2. Cumulative incidence of thrombotic and hemorrhagic complications [ Time Frame: 1 month ]
   Cumulative incidence of thrombotic and hemorrhagic complications List according to PT1 protocol.
3. Deaths and causes [ Time Frame: 1 month ]
   Deaths and causes
4. Analysis of the results of VGTCO and VGTi [ Time Frame: 1 month ]
   Analysis of the results of VGTCO and VGTi as a function of hemoglobin and hematocrit

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Loïc GARCON, professor; +33 322 087 056; garcon.loic@chu-amiens.fr

Contact: Mohamed AIT AMER MEZIANE, Phd; +33 322 088 384; aitamermeziane.mohamed@chu-amiens.fr

Sponsors and Collaborators

Centre Hospitalier Universitaire, Amiens

Investigators

• Study Director: Loïc GARCON, professor; CHU Amiens-Picardie
• Principal Investigator: Lydia ROY, Doctor; CHU Henri Mondor, France
• Principal Investigator: Marjolaine GEORGES, Doctor; Centre Hospitalier Universitaire Dijon

More Information

• Responsible Party: Centre Hospitalier Universitaire, Amiens
• ClinicalTrials.gov Identifier: NCT03008642
• Other Study ID Numbers: PI2016_843_0032
• First Posted: January 2, 2017
• Last Update Posted: February 4, 2019
• Last Verified: February 2019

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

Keywords provided by Centre Hospitalier Universitaire, Amiens:

Polycythemia; CO-Rebreathing; red cell mass determination; myeloproliferative neoplasms

Additional relevant MeSH terms:

Polycythemia; Hematologic Diseases