Clinical trial NCT04081012: N-acetyl Cysteine in Post-reperfusion Pulmonary Injury in Chronic Thromboembolic Pulmonary Hypertension.
Official title: N-acetyl Cysteine in Post-reperfusion Pulmonary Injury in Patients With Chronic Thromboembolic Pulmonary Hypertension Undergoing Pulmonary Balloon Angioplasty and Pulmonary Endarterectomy.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Chronic Thromboembolic Pulmonary Hypertension
Lead sponsor: Instituto Nacional de Cardiologia Ignacio Chavez
Sponsor class: OTHER
First posted: 2019-09-06
Enrollment: 34
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind clinical trial of the treatment will be the treating physician and radiologist, of parallel groups in patients undergoing EAP and BPA.
Primary purpose: TREATMENT

Brief summary: This study will evaluate the use of N-acetyl cysteine in post-reperfusion pulmonary injury in patients with chronic thromboembolic pulmonary hypertension undergoing pulmonary balloon angioplasty and pulmonary endarterectomy. Half of the patients will receive N-acetyl cysteine and the other placebo.

Detailed description: For chronic pulmonary embolism thrombus hypertension, the potentially curative treatment is endarterectomy, however in 12 to 60% it does not present surgical susceptibility, so pulmonary balloon angioplasty is the secondary option. In these procedures the complication that occurs most frequently is pulmonary oedema after reperfusion is a frequent complication (17.8-65%), appears between 24-72 hours after the intervention and the diagnosis is made in the presence of infiltrate interstitial in chest radiography or computed tomography of the chest. Initially it was believed that it was difficult due to the increase in perfusion of secondary flow in the territory due to pulmonary vascular dilation, it is now believed that microtraumatism is involved by the guides and balloon used, vascular dysfunction and cytokines and innate immunity and adaptive, complement activation, coagulation cascade activation, apoptosis pathway activation, endothelial dysfunction caused by reperfusion contribute to cell dysfunction.

The use of N-acetyl cysteine for its antioxidant properties, inflammatory response attenuator, reduction of reactive oxygen species (ROS) and that in addition to having already had to reduce the condition of decrease in post-reperfusion ischemia15,16 in other situations is a viable option in the treatment of acute post-reperfusion edema in patients sometimes a pulmonary endarterectomy and balloon pulmonary angioplasty.

Eligibility criteria: Inclusion Criteria:

- Patients who are diagnosed with group 4 pulmonary hypertension and are susceptible to pulmonary endarterectomy or balloon angioplasty in patients over 18 years.

Exclusion Criteria:

* Patients who do not accept admission to the trial.
* Presence of arterial hypotension or sepsis.

Primary outcomes:
measure: Presence of Post-reperfusion pulmonary injury.
timeFrame: 72 hours
Secondary outcomes:
measure: Concentration of cytokines (pg/ml)
timeFrame: Basal and at 72 hours
measure: Percentaje of Complications (%)
timeFrame: 30 days
Other outcomes:
Locations:
city: Ciudad de mexico
country: Mexico
facility: Instituto Nacional Ignacio Chavez
Study officials:
affiliation: Instituto Nacional de Cardiología "Ignacio Chávez"
name: Maria Elena Soto Lopez
role: PRINCIPAL_INVESTIGATOR
References:
citation: Konstantinides SV, Barco S, Lankeit M, Meyer G. Management of Pulmonary Embolism: An Update. J Am Coll Cardiol. 2016 Mar 1;67(8):976-990. doi: 10.1016/j.jacc.2015.11.061.
citation: Huisman MV, Barco S, Cannegieter SC, Le Gal G, Konstantinides SV, Reitsma PH, Rodger M, Vonk Noordegraaf A, Klok FA. Pulmonary embolism. Nat Rev Dis Primers. 2018 May 17;4:18028. doi: 10.1038/nrdp.2018.28.
citation: Pengo V, Lensing AW, Prins MH, Marchiori A, Davidson BL, Tiozzo F, Albanese P, Biasiolo A, Pegoraro C, Iliceto S, Prandoni P; Thromboembolic Pulmonary Hypertension Study Group. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med. 2004 May 27;350(22):2257-64. doi: 10.1056/NEJMoa032274.
citation: Ogawa A, Satoh T, Fukuda T, Sugimura K, Fukumoto Y, Emoto N, Yamada N, Yao A, Ando M, Ogino H, Tanabe N, Tsujino I, Hanaoka M, Minatoya K, Ito H, Matsubara H. Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension: Results of a Multicenter Registry. Circ Cardiovasc Qual Outcomes. 2017 Nov;10(11):e004029. doi: 10.1161/CIRCOUTCOMES.117.004029.
citation: Wilkens H, Lang I, Behr J, Berghaus T, Grohe C, Guth S, Hoeper MM, Kramm T, Kruger U, Langer F, Rosenkranz S, Schafers HJ, Schmidt M, Seyfarth HJ, Wahlers T, Worth H, Mayer E. Chronic thromboembolic pulmonary hypertension (CTEPH): updated Recommendations of the Cologne Consensus Conference 2011. Int J Cardiol. 2011 Dec;154 Suppl 1:S54-60. doi: 10.1016/S0167-5273(11)70493-4.
citation: Laubach VE, Sharma AK. Mechanisms of lung ischemia-reperfusion injury. Curr Opin Organ Transplant. 2016 Jun;21(3):246-52. doi: 10.1097/MOT.0000000000000304.
citation: Zabini D, Heinemann A, Foris V, Nagaraj C, Nierlich P, Balint Z, Kwapiszewska G, Lang IM, Klepetko W, Olschewski H, Olschewski A. Comprehensive analysis of inflammatory markers in chronic thromboembolic pulmonary hypertension patients. Eur Respir J. 2014 Oct;44(4):951-62. doi: 10.1183/09031936.00145013. Epub 2014 Jul 17.
citation: Sun Y, Pu LY, Lu L, Wang XH, Zhang F, Rao JH. N-acetylcysteine attenuates reactive-oxygen-species-mediated endoplasmic reticulum stress during liver ischemia-reperfusion injury. World J Gastroenterol. 2014 Nov 7;20(41):15289-98. doi: 10.3748/wjg.v20.i41.15289.
citation: Geudens N, Wuyts WA, Rega FR, Vanaudenaerde BM, Neyrinck AP, Verleden GM, Lerut TE, Van Raemdonck DE. N-acetyl cysteine attenuates the inflammatory response in warm ischemic pig lungs. J Surg Res. 2008 May 15;146(2):177-83. doi: 10.1016/j.jss.2007.05.018. Epub 2007 Jul 20.