Clinical trial NCT00434902: Evaluation of the Prevalence of Pulmonary Hypertension in Adult Patients With Sickle Cell Disease
Official title: Evaluation of the Characteristics, Prevalence and Prognosis of Pulmonary Hypertension in Adult Patients With Sickle Cell Disease: Study ETENDARD.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Sickle Cell Disease
Keywords: Doppler Echocardiography
Pulmonary hypertension
Sickle cell disease
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2007-02-14
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult Patients With Sickle Cell Disease

Brief summary: Recent data show that pulmonary hypertension (PH), defined by a tricuspid regurgitation jet (TRJ) velocity \> or equal at 2.5m/s on Doppler echocardiography, is present in about 30% of adults with sickle cell disease (SCD) and is associated with poor prognosis. However in SCD the occurrence of PH (defined by mean pulmonary arterial pressure (mPAP)\> or equal at 25 mmHg) is related to at least 3 mechanisms: PH due to hyperkinetic state with high cardiac output (CO) but normal pulmonary vascular resistance (PVR \<160 dynes), or postcapillary PH (pulmonary capillary wedge pressure PCWP \>15 mmHg), or precapillary pulmonary arterial hypertension (PAH) defined by mPAP \> or equal at 25 mmHg, PCWP\< or equal at 15 mmHg and PVR \> or equal at 160 dynes.The aim of this study is to evaluate in a French population of adults with sickle cell disease the characteristics, prevalence and prognosis of pulmonary hypertension.

Detailed description: Consecutive adult patients with sickle cell disease (SCD) had a Doppler echocardiography to evaluate if they had a suspected pulmonary hypertension (PH) on the basis of a tricuspid regurgitation jet (TRJ) velocity \> or equal at 2.5m/s. In this case, a right heart catheterization was performed to confirm or not this diagnosis and its mechanisms. Each included patient was followed every year for 3 years: during each visit, a clinical evaluation was obtained and a Doppler echocardiography. In case of emergence of a suspected PH, a right heart catheterization was performed to confirm or not this diagnosis and its mechanisms.

Three groups of patients were defined: no PH, precapillary PH, and a third group including post-capillary PH and hyperkinetic state. These groups were well defined on the basis of the results of th Doppler echocardiography and right heart catheterisation.

Characteristics of patients and their prognosis were evaluated in each group.

In the same, way, biological study is planned to evaluate some biological markers of the mechanism of PH, and prognostic factors.

Eligibility criteria: Inclusion Criteria:

* Homozygous SS sickle cell disease
* Male or female \> 18 years of age
* VOC (Vaso-Occlusive crisis) or ACS (Acute chest syndrome)within 6 weeks of inclusion ("Stable state")
* Signed written Informed consent

Exclusion Criteria:

* Creatinine clearance \< 30 ml/mn
* prothrombin ratio \< 50%
* Severe pneumopathy and TLC (Total lung capacity) \< 70%

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Clamart
country: France
facility: Hôpital Antoine Béclère
Study officials:
affiliation: Hôpital Antoine Béclère, CLAMART
name: Gerald SIMONNEAU, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Henri Mondor, Creteil
name: Frederic Galacteros, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Henri Mondor, CRETEIL
name: Serge ADNOT, MD
role: STUDY_DIRECTOR
affiliation: Hopital Henri Mondor, CRETEIL
name: Bernard MAITRE, MD
role: STUDY_DIRECTOR
affiliation: Hôpîtal Antoine Béclere, CLAMART
name: Marc HUMBERT, MD
role: STUDY_DIRECTOR
affiliation: Hôpital Tenon, PARIS
name: Robert GIROT, MD
role: STUDY_DIRECTOR
affiliation: Hôpital TENON, PARIS
name: François LIONNET, MD
role: STUDY_DIRECTOR
affiliation: Hôpital Bicêtre, KREMLIN BICETRE
name: Françoise DRISS, MD
role: STUDY_DIRECTOR
affiliation: Hôpital Bicêtre, KREMLIN BICETRE
name: Olivier LAMBOTTE, MD
role: STUDY_CHAIR
affiliation: CHU Fort de France
name: Jocelyn INAMO, MD
role: STUDY_DIRECTOR
affiliation: CHU Fort de France
name: Gylna LOKO, MD
role: STUDY_DIRECTOR
affiliation: Hôpital Antoine Béclère, CLAMART
name: Olivier SITBON, MD
role: STUDY_DIRECTOR
affiliation: Hôpital Antoine Béclère, CLAMART
name: Xavier Jaïs, MD
role: STUDY_DIRECTOR
affiliation: Hôpital Henri Mondor, CRETEIL
name: Anoosha Habibi, MD
role: STUDY_CHAIR
affiliation: Hôpital Henri Mondor, CRETEIL
name: Dora Bachir, MD
role: STUDY_CHAIR
affiliation: Hopital Henri Mondor, CRETEIL
name: Laurent SAVALE, MD
role: STUDY_CHAIR
affiliation: Hôpital Henri Mondor, CRETEIL
name: Saadia Eddahibi, MD
role: STUDY_CHAIR
affiliation: Hopital Antoine Béclère, CLAMART
name: Gilles Garcia, MD
role: STUDY_CHAIR
References:
citation: Simonneau G, Galie N, Rubin LJ, Langleben D, Seeger W, Domenighetti G, Gibbs S, Lebrec D, Speich R, Beghetti M, Rich S, Fishman A. Clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2004 Jun 16;43(12 Suppl S):5S-12S. doi: 10.1016/j.jacc.2004.02.037.
citation: Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, Keogh A, Pulido T, Frost A, Roux S, Leconte I, Landzberg M, Simonneau G. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002 Mar 21;346(12):896-903. doi: 10.1056/NEJMoa012212.
citation: Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004 Sep 30;351(14):1425-36. doi: 10.1056/NEJMra040291. No abstract available.
citation: Lechapt E, Habibi A, Bachir D, Galacteros F, Schaeffer A, Desvaux D, Brochard L, Housset B, Godeau B, Maitre B. Induced sputum versus bronchoalveolar lavage during acute chest syndrome in sickle cell disease. Am J Respir Crit Care Med. 2003 Dec 1;168(11):1373-7. doi: 10.1164/rccm.200302-174OC. Epub 2003 Sep 11.
citation: Maitre B, Habibi A, Roudot-Thoraval F, Bachir D, Belghiti DD, Galacteros F, Godeau B. Acute chest syndrome in adults with sickle cell disease. Chest. 2000 May;117(5):1386-92. doi: 10.1378/chest.117.5.1386.
citation: Parent F, Bachir D, Inamo J, Lionnet F, Driss F, Loko G, Habibi A, Bennani S, Savale L, Adnot S, Maitre B, Yaici A, Hajji L, O'Callaghan DS, Clerson P, Girot R, Galacteros F, Simonneau G. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med. 2011 Jul 7;365(1):44-53. doi: 10.1056/NEJMoa1005565.