ZODIAC: Benefit of One Month Zopiclone Intake on Adaptative Servoventilation Compliance
Study Details
Study Description
Brief Summary
The study evaluate the effect of adaptative servoventilation (ASV) initiation combined with 14 days Zopiclone vs Placebo treatment in patients with central sleep apnea (CSA) syndrome.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
Detailed Description
ASV remain the optimal treatment for CSA in Heart Failure patients with preserved left ventricular ejection fraction (LVEF).
Yet, the adaptation to the ventilation is extremely challenging and the resulting difficulties encountered to sleep induction might be a reason for dropping out.
Zopiclone is indicated for the short-term treatment of insomnia where sleep initiation or sleep maintenance are prominent symptoms. In this study, Zopiclone, as sedative and hypnotic agent, is used during the ASV initiation period.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: ZOPICLONE Zopiclone 3.5 mg capsule by mouth daily for 2 weeks |
Drug: Zopiclone
Other Names:
|
Placebo Comparator: PLACEBO Placebo 3.5 mg capsule by mouth daily for 2 weeks |
Drug: Placebo
|
Outcome Measures
Primary Outcome Measures
- Average use of the Adapative Servo Ventilation device per day assessed by the device data [one month]
daily use of the device (hours/day, mean value), amount of hours and number of day the device has been used as assessed by the device data
Secondary Outcome Measures
- Average use of the Adapative Servo Ventilation device per day assessed by the device data [3 months and 12 months]
- Residual Apnea, Hypopnea Index (number/hour) [12 months]
Index assessed by device data
- Daytime sleepiness assessed by the Epworth Sleepiness Scale (ESS) [1 month]
- Daytime sleepiness assessed by the Epworth Sleepiness Scale (ESS) [3 months]
- Daytime sleepiness assessed by the Epworth Sleepiness Scale (ESS) [12 month]
- Asthenia assessed by Pichot scale [1 month]
- Asthenia assessed by Pichot scale [3 months]
- Asthenia assessed by Pichot scale [12 months]
- Changes in New York Heart Association score [1 month]
- Changes in New York Heart Association score [3 months]
- Changes in New York Heart Association score [12 months]
- Number of prescription of hypnotics drug [12 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female aged between 18 and 90 years at the initial visit
-
Central Sleep Apnea with an AHI ≥ 15/h and at least 50% of central events indicating an ASV therapy, as determined by a ventilatory polygraphy (PG) or a polysomnography (PSG)
-
Cardiac Dysfunction with Left Ventricular Ejection fraction(LVEF)> 45% determined by a transthoracic echocardiography (TTE), known for more than 12 weeks and stable for at least 4 weeks;
-
Compliance less than 3 hours after 7 days of the setting up of ASV;
-
Patient affiliated to a social security scheme or being beneficiary of such scheme;
-
Patient voluntarily participating in the research, with written informed consent
Exclusion Criteria:
-
Current use of continuous positive airway pressure (cPAP) for treatment of sleep apnea during the last 12 months
-
Presence of chronic symptomatic heart failure with reduced left ventricular ejection fraction (LVEF ≤ 45%), and a CSA moderate to severe (AHI ≥15 / h)
-
Presence of severe pulmonary bullous disease
-
Presence of Pneumothorax or pneumomediastinum
-
Hypotension, especially if associated with depletion of intravascular volume
-
Dehydration
-
Leaking of cerebrospinal fluid, cranial surgery or trauma recently.
-
Episode of acute respiratory failure or heart failure in the previous month
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Clinique de Physiologie Sommeil et Exercice, Pole Thorax et Vaisseaux , University Hospital Grenoble Alpes | Grenoble | France | 38043 |
Sponsors and Collaborators
- University Hospital, Grenoble
Investigators
- Principal Investigator: Marie DESTORS, MD, University Hospital, Grenoble Alpes, FRANCE
Study Documents (Full-Text)
None provided.More Information
Publications
- Adam SS, Key NS, Greenberg CS. D-dimer antigen: current concepts and future prospects. Blood. 2009 Mar 26;113(13):2878-87. doi: 10.1182/blood-2008-06-165845. Epub 2008 Nov 13. Review.
- Blohmé G. Treatment of hereditary angioneurotic oedema with tranexamic acid. A random double-blind cross-over study. Acta Med Scand. 1972 Oct;192(4):293-8.
- Boccon-Gibod I, Bouillet L. [Angioedema and urticaria]. Ann Dermatol Venereol. 2014 Nov;141 Suppl 3:S586-95. doi: 10.1016/S0151-9638(14)70162-0. Review. French.
- Bork K, Steffensen I, Machnig T. Treatment with C1-esterase inhibitor concentrate in type I or II hereditary angioedema: a systematic literature review. Allergy Asthma Proc. 2013 Jul-Aug;34(4):312-27. doi: 10.2500/aap.2013.34.3677. Epub 2013 May 22. Review.
- Bouillet L, Mannic T, Arboleas M, Subileau M, Massot C, Drouet C, Huber P, Vilgrain I. Hereditary angioedema: key role for kallikrein and bradykinin in vascular endothelial-cadherin cleavage and edema formation. J Allergy Clin Immunol. 2011 Jul;128(1):232-4. doi: 10.1016/j.jaci.2011.02.017. Epub 2011 Mar 24.
- Bouillet L, Sidibé A, Polena H, Mannic T, Deroux A, Stidder B, Vittecoq O, Vilgrain I. [Endothelial junctions: exploiting their instability in the development of biomarkers for vascular remodelling]. Med Sci (Paris). 2014 Jun-Jul;30(6-7):633-5. doi: 10.1051/medsci/20143006012. Epub 2014 Jul 11. French.
- Bouillet L, Vilgrain I. VE-cadherin, a potential marker for endothelial cell activation during hereditary angioedema attacks. J Allergy Clin Immunol. 2014 Jul;134(1):241. doi: 10.1016/j.jaci.2014.04.016. Epub 2014 May 27.
- Brevet: w/o 2008 062314 circulating ve-cadherin as a predictive marker of sensitivity or resistance to anti-tumoral treatment, and improved method for the detection of soluble proteins.
- Brickman CM, Frank MM, Kaliner M. Urine-histamine levels in patients with hereditary angioedema (HAE). J Allergy Clin Immunol. 1988 Sep;82(3 Pt 1):403-6.
- Brown NJ, Gainer JV, Stein CM, Vaughan DE. Bradykinin stimulates tissue plasminogen activator release in human vasculature. Hypertension. 1999 Jun;33(6):1431-5.
- Bygum A. Hereditary angio-oedema in Denmark: a nationwide survey. Br J Dermatol. 2009 Nov;161(5):1153-8. doi: 10.1111/j.1365-2133.2009.09366.x. Epub 2009 Jun 22.
- Cugno M, Hack CE, de Boer JP, Eerenberg AJ, Agostoni A, Cicardi M. Generation of plasmin during acute attacks of hereditary angioedema. J Lab Clin Med. 1993 Jan;121(1):38-43.
- Cugno M, Zanichelli A, Bellatorre AG, Griffini S, Cicardi M. Plasma biomarkers of acute attacks in patients with angioedema due to C1-inhibitor deficiency. Allergy. 2009 Feb;64(2):254-7. doi: 10.1111/j.1398-9995.2008.01859.x. Epub 2008 Dec 4.
- Deroux A, Vilgrain I, Dumestre-Pérard C, Boccon-Gibod I, Bouillet L. Towards a specific marker for acute bradykinin-mediated angioedema attacks: a literature review. Eur J Dermatol. 2015 Jul-Aug;25(4):290-5. doi: 10.1684/ejd.2015.2547. Review.
- Dinkel HP, Maroske J, Schrod L. Sonographic appearances of the abdominal manifestations of hereditary angioedema. Pediatr Radiol. 2001 Apr;31(4):296-8.
- El-Hachem C, Amiour M, Guillot M, Laurent J. [Hereditary angioneurotic edema: a case report in a 3-year-old child]. Arch Pediatr. 2005 Aug;12(8):1232-6. French.
- Farkas H. Management of upper airway edema caused by hereditary angioedema. Allergy Asthma Clin Immunol. 2010 Jul 28;6(1):19. doi: 10.1186/1710-1492-6-19.
- Farkas H. Pediatric hereditary angioedema due to C1-inhibitor deficiency. Allergy Asthma Clin Immunol. 2010 Jul 28;6(1):18. doi: 10.1186/1710-1492-6-18.
- Frank MM, Sergent JS, Kane MA, Alling DW. Epsilon aminocaproic acid therapy of hereditary angioneurotic edema. A double-blind study. N Engl J Med. 1972 Apr 13;286(15):808-12.
- Fujii K, Konishi K, Kanno Y, Ohgou N. Acute urticaria with elevated circulating interleukin-6 is resistant to anti-histamine treatment. J Dermatol. 2001 May;28(5):248-50.
- Ghannam A, Sellier P, Defendi F, Favier B, Charignon D, López-Lera A, López-Trascasa M, Ponard D, Drouet C. C1 inhibitor function using contact-phase proteases as target: evaluation of an innovative assay. Allergy. 2015 Sep;70(9):1103-11. doi: 10.1111/all.12657. Epub 2015 Jun 9.
- Hogan AD, Schwartz LB. Markers of mast cell degranulation. Methods. 1997 Sep;13(1):43-52.
- Joseph K, Tholanikunnel BG, Wolf B, Bork K, Kaplan AP. Deficiency of plasminogen activator inhibitor 2 in plasma of patients with hereditary angioedema with normal C1 inhibitor levels. J Allergy Clin Immunol. 2016 Jun;137(6):1822-1829.e1. doi: 10.1016/j.jaci.2015.07.041. Epub 2015 Sep 26.
- Kahn R, Herwald H, Müller-Esterl W, Schmitt R, Sjögren AC, Truedsson L, Karpman D. Contact-system activation in children with vasculitis. Lancet. 2002 Aug 17;360(9332):535-41.
- Kaplan AP, Austen KF. A prealbumin activator of prekallikrein. II. Derivation of activators of prekallikrein from active Hageman factor by digestion with plasmin. J Exp Med. 1971 Apr 1;133(4):696-712.
- Kasperska-Zajac A, Brzoza Z. Increased D-dimer concentration in plasma of patients with severe acute urticaria. Br J Dermatol. 2009 Dec;161(6):1409-10. doi: 10.1111/j.1365-2133.2009.09466.x. Epub 2009 Sep 15.
- Kasperska-Zając A, Grzanka A, Czecior E, Misiolek M, Rogala B, Machura E. Acute phase inflammatory markers in patients with non-steroidal anti-inflammatory drugs (NSAIDs)-induced acute urticaria/angioedema and after aspirin challenge. J Eur Acad Dermatol Venereol. 2013 Aug;27(8):1048-52. doi: 10.1111/j.1468-3083.2012.04486.x. Epub 2012 Feb 21.
- Kleniewski J, Blankenship DT, Cardin AD, Donaldson V. Mechanism of enhanced kinin release from high molecular weight kininogen by plasma kallikrein after its exposure to plasmin. J Lab Clin Med. 1992 Jul;120(1):129-39.
- Kluft C, Trumpi-Kalshoven MM, Jie AF, Veldhuyzen-Stolk EC. Factor XII-dependent fibrinolysis: a double function of plasma kallikrein and the occurrence of a previously undescribed factor XII- and kallikrein-dependent plasminogen proactivator. Thromb Haemost. 1979 Jun 30;41(4):756-73.
- MacGinnitie AJ. Pediatric hereditary angioedema. Pediatr Allergy Immunol. 2014 Aug;25(5):420-7. doi: 10.1111/pai.12168. Epub 2013 Dec 9. Review.
- Nielsen EW, Johansen HT, Høgåsen K, Wuillemin W, Hack CE, Mollnes TE. Activation of the complement, coagulation, fibrinolytic and kallikrein-kinin systems during attacks of hereditary angioedema. Scand J Immunol. 1996 Aug;44(2):185-92.
- Nussberger J, Cugno M, Cicardi M. Bradykinin-mediated angioedema. N Engl J Med. 2002 Aug 22;347(8):621-2.
- Pagnier A. [Hereditary angioedema in childhood. Diagnosis and therapeutic challenges]. Presse Med. 2015 Jan;44(1):89-95. doi: 10.1016/j.lpm.2014.07.018. Epub 2014 Dec 12. Review. French.
- Payne V, Kam PC. Mast cell tryptase: a review of its physiology and clinical significance. Anaesthesia. 2004 Jul;59(7):695-703. Review.
- Pritzker HA, Levin TL, Weinberg G. Recurrent colocolic intussusception in a child with hereditary angioneurotic edema: reduction by air enema. J Pediatr Surg. 2004 Jul;39(7):1144-6.
- Reshef A, Zanichelli A, Longhurst H, Relan A, Hack CE. Elevated D-dimers in attacks of hereditary angioedema are not associated with increased thrombotic risk. Allergy. 2015 May;70(5):506-13. doi: 10.1111/all.12587. Epub 2015 Feb 23.
- Sanchez A, Ecochard A, Maestracci M, Rodiere M. [Hereditary angioedema causing colocolic intussusception]. Arch Pediatr. 2008 Mar;15(3):271-4. doi: 10.1016/j.arcped.2007.12.004. Epub 2008 Mar 10. French.
- Sidibé A, Polena H, Pernet-Gallay K, Razanajatovo J, Mannic T, Chaumontel N, Bama S, Maréchal I, Huber P, Gulino-Debrac D, Bouillet L, Vilgrain I. VE-cadherin Y685F knock-in mouse is sensitive to vascular permeability in recurrent angiogenic organs. Am J Physiol Heart Circ Physiol. 2014 Aug 1;307(3):H455-63. doi: 10.1152/ajpheart.00774.2013. Epub 2014 May 23.
- Sidibé A, Polena H, Razanajatovo J, Mannic T, Chaumontel N, Bama S, Maréchal I, Huber P, Gulino-Debrac D, Bouillet L, Vilgrain I. Dynamic phosphorylation of VE-cadherin Y685 throughout mouse estrous cycle in ovary and uterus. Am J Physiol Heart Circ Physiol. 2014 Aug 1;307(3):H448-54. doi: 10.1152/ajpheart.00773.2013. Epub 2014 May 23.
- Suffritti C, Zanichelli A, Maggioni L, Bonanni E, Cugno M, Cicardi M. High-molecular-weight kininogen cleavage correlates with disease states in the bradykinin-mediated angioedema due to hereditary C1-inhibitor deficiency. Clin Exp Allergy. 2014 Dec;44(12):1503-14. doi: 10.1111/cea.12293.
- 38RC15.175