Extrathoracic Sarcoidosis Clinical Trial
— EFIRTESOfficial title:
Efficacy of Remission-induction Regimen With Infliximab for Severe Extrathoracic Sarcoidosis (EFIRTES STUDY)
| Verified date | October 2023 |
| Source | Assistance Publique - Hôpitaux de Paris |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The present study was designed to assess the efficacy of infliximab in a 2-period study : - An initial period with comparison of infliximab versus placebo and allowing the determination of the primary criteria - Then an extension period in which the 2 arms will receive infliximab (in the placebo group : 5 perfusions and in the experimental group 3 supplemental perfusions). Finally, the 2 groups will receive 5 injections of infliximab There is little evidence in the literature of when and how infliximab should be administered in sarcoidosis. We hypothesized, from our personal experience in 30 cases (18 of which were reported in a retrospective trial (14), that infliximab would have a very quick activity. So it appeared reasonable to evaluate the primary criterion at 6 weeks after initiation of the treatment.
| Status | Completed |
| Enrollment | 31 |
| Est. completion date | September 28, 2021 |
| Est. primary completion date | June 21, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Clinical and radiological presentation confirming sarcoidosis - Presence of non caseating granuloma in at least one organ - Presence of at least one extrathoracic localization, including hypercalcemia - Exclusion of other causes of granuloma - Presence of serious organ involvement or relapse/apparition of a new localization despite a first-line immunosuppressive drug - Age superior or equal to 18 years Exclusion Criteria: - Pregnancy or breast feeding or women in age of pregnancy without efficient contraception - Patients with multiple sclerosis - Patients with prior history of any cancer in the 5 years before inclusion (except for cutaneous basocellular cancers), - Patients with a history of hypersensitivity to infliximab to other murine proteins, or to any of the excipients - Patients with untreated tuberculosis or current other severe infections such as sepsis, abscesses, and opportunistic infections• Patients with moderate or severe heart failure (NYHA class III/IV) - Concurrent vaccination with live vaccines during therapy - Inability to understand information about the protocol - Adult subject under legal protection or unable to consent. - No informed consent - Absence of affiliation to National French social security system - Patients with severe renal failure, severe hepatic impairment, hepatocellular insufficiency, chronic respiratory insufficiency, risk of angle closure glaucoma, risk of urinary retention related to urethroprostatic disorders, certain evolving viral diseases (including hepatitis, herpes, varicella, zoster), psychotic states still not controlled by treatment |
| Country | Name | City | State |
|---|---|---|---|
| France | Hopital Avicenne - service de pnaumologie | Bobigny | |
| France | Hopital Henri Mondor- service de Médecine Interne | Créteil | |
| France | Hopital Claude Huriez- service de Médecine Interne | Lille | |
| France | Hopital de la Croix Rousse- service de Médecine Interne | Lyon | |
| France | Hopital de la Timone- service de Médecine Internne | Marseille | |
| France | CHU Hotel Dieu - service de Médecine Interne | Nantes | |
| France | GH la Pitié Salpêtrière. Service de Médecine interne | Paris | |
| France | Hopital BICHAT - Médecine Interne | Paris | |
| France | Hopital Bichat- service de pneumologie | Paris | |
| France | Nouvel Hopital Civil- service de Médecine Interne | Strasbourg |
| Lead Sponsor | Collaborator |
|---|---|
| Assistance Publique - Hôpitaux de Paris |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Percentage of patients | who have a severity assessment score (ePOST score) inferior to 1 in all organs and absence of hypercalcemia at W6, whatever the corticosteroid dosage received | week 6 | |
| Secondary | Percentage of patients | who will have completed the steroid tapering regimen, will have a severity assessment score (ePOST score) < 1 in all organs, absence of hypercalcemia, had not have a relapse or any reason for treatment failure | week 16 for experimental arm ; week 22 for control arm | |
| Secondary | Mean variation in severity assessment score measured by extrapulmonary Physician Organ Severity Tool (ePOST) | ePOST score will be assessed by the physician in charge of the patient. This score reflects the sarcoidosis activity in 17 organs and has been validated in previous studies : Skin, Peripheral lymph nodes, Eyes, Liver, Spleen, Central nervous system, Peripheral nervous system, Parotid/salivary glands, Bone marrow, Ear, Nose, Throat, Cardiac, Renal, Bone/joint, Muscle, Gastrointestinal. For each organ, a score will : 0 as Not affected, 1 as Slight, 2 as Mild, 3 as Moderate, 4 as Moderate to severe, 5 as Severe and 6 as Very severe. Total score is the sum of score in each organ. | Week 6 | |
| Secondary | Pulmonary sarcoidosis involvement | Pulmonary sarcoidosis involvement will be assessed by the physician in charge of the patient rated as: 0 as Not affected, 1 as Slight, 2 as Mild, 3 as Moderate, 4 as Moderate to severe, 5 as Severe and 6 as Very severe. | Week 6 | |
| Secondary | Pulmonary sarcoidosis involvement 2 weeks after the 5th injection | Pulmonary sarcoidosis involvement will be assessed by the physician in charge of the patient rated as: 0 as Not affected, 1 as Slight, 2 as Mild, 3 as Moderate, 4 as Moderate to severe, 5 as Severe and 6 as Very severe. | week 16 for experimental arm ; week 22 for control arm | |
| Secondary | Severity assessment score measured by ePOST 2 weeks after the 5th injection | ePOST score will be assessed by the physician in charge of the patient. This score reflects the sarcoidosis activity in 17 organs and has been validated in previous studies : Skin, Peripheral lymph nodes, Eyes, Liver, Spleen, Central nervous system, Peripheral nervous system, Parotid/salivary glands, Bone marrow, Ear, Nose, Throat, Cardiac, Renal, Bone/joint, Muscle, Gastrointestinal. For each organ, a score will : 0 as Not affected, 1 as Slight, 2 as Mild, 3 as Moderate, 4 as Moderate to severe, 5 as Severe and 6 as Very severe. Total score is the sum of score in each organ | week 16 for experimental arm ; week 22 for control arm | |
| Secondary | Mean variation in the severity assessment score measured by ePOST from 1st injection (W0 or W6) to 2 weeks after the 5th injection | ePOST score will be assessed by the physician in charge of the patient. This score reflects the sarcoidosis activity in 17 organs and has been validated in previous studies : Skin, Peripheral lymph nodes, Eyes, Liver, Spleen, Central nervous system, Peripheral nervous system, Parotid/salivary glands, Bone marrow, Ear, Nose, Throat, Cardiac, Renal, Bone/joint, Muscle, Gastrointestinal. For each organ, a score will : 0 as Not affected, 1 as Slight, 2 as Mild, 3 as Moderate, 4 as Moderate to severe, 5 as Severe and 6 as Very severe. Total score is the sum of score in each organ. | week 16 for experimental arm ; week 22 for control arm | |
| Secondary | Mean variation of quality of life measured by SF-36 | The SF-36 questionnaire is a quality of life questionnaire that includes 36 questions divided into 8 different categories (physical functioning, limitations due to physical condition, physical pain, perceived health, vitality, social functioning or well-being, limitations due to mental condition, mental health). It is self-administered and takes less than 10 minutes. Higher scores indicate better quality of life. Score from 0 to 100. | Week 6 | |
| Secondary | Mean variation of fatigue, measured by the Fatigue Scale (FAS) | The total score ranges from 10 to 50. A total FAS score < 22 indicates no fatigue, a score = 22 indicates fatigue | Week 6 | |
| Secondary | Mean variation of quality of life measured by SF-36 | The SF-36 questionnaire is a quality of life questionnaire that includes 36 questions divided into 8 different categories (physical functioning, limitations due to physical condition, physical pain, perceived health, vitality, social functioning or well-being, limitations due to mental condition, mental health). It is self-administered and takes less than 10 minutes. Higher scores indicate better quality of life. Score from 0 to 100. | week 16 for experimental arm ; week 22 for control arm | |
| Secondary | Mean variation of fatigue, measured by the Fatigue Scale (FAS) | The total score ranges from 10 to 50. A total FAS score < 22 indicates no fatigue, a score = 22 indicates fatigue | week 16 for experimental arm ; week 22 for control arm | |
| Secondary | Rate of relapses | A relapse will be defined by the apparition of a new localization or a majoration of the severity assessment score from the previous assessment in at least one organ among the 17 studied in the ePOST score, after a previous 1 point or more decrease without hypercalcemia. | week 16 for experimental arm ; week 22 for control arm |