N-acetyl Cysteine in Post-reperfusion Pulmonary Injury in Chronic Thromboembolic Pulmonary Hypertension.

Chronic Thromboembolic Pulmonary Hypertension Clinical Trial

— NAC-PostRep  

Official title:

N-acetyl Cysteine in Post-reperfusion Pulmonary Injury in Patients With Chronic Thromboembolic Pulmonary Hypertension Undergoing Pulmonary Balloon Angioplasty and Pulmonary Endarterectomy.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04081012
• Other study ID #: 191110
• Status: Recruiting
• Phase: N/A
• Start date: May 21, 2019
• Est. completion date: May 21, 2023

Study information

• Verified date: September 2020
• Source: Instituto Nacional de Cardiologia Ignacio Chavez
• Contact: Maria Elena Soto Lopez, Dr.
• Phone: 5538808997
• Email: mesoto50[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 34
• Est. completion date: May 21, 2023
• Est. primary completion date: May 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Thromboembolic Pulmonary Hypertension
• Hypertension
• Hypertension, Pulmonary
• Lung Injury

Intervention

Drug:
• N-acetyl cysteine
Patients will receive a 4-dose schedule of 600 mg diluted in 50 ml of 0.9% saline intravenously every 12 hours starting 24 hours before pulmonary endarterectomy or balloon pulmonary angioplasty.
• Placebo
The placebo group will receive a similar volume of normal saline as a placebo at the same time intervals.

Locations

Country	Name	City	State
Mexico	Instituto Nacional Ignacio Chavez	Ciudad de mexico

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Cardiologia Ignacio Chavez

Country where clinical trial is conducted

Mexico, 

References & Publications (9)

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. Epub 2007 Jul 20. — View 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. Review. — View Citation

Konstantinides SV, Barco S, Lankeit M, Meyer G. Management of Pulmonary Embolism: An Update. J Am Coll Cardiol. 2016 Mar 1;67(8):976-90. doi: 10.1016/j.jacc.2015.11.061. Review. — View 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. Review. — View 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). pii: e004029. doi: 10.1161/CIRCOUTCOMES.117.004029. — View 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. — View 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. — View Citation

Wilkens H, Lang I, Behr J, Berghaus T, Grohe C, Guth S, Hoeper MM, Kramm T, Krüger U, Langer F, Rosenkranz S, Schäfers 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. — View Citation

Zabini D, Heinemann A, Foris V, Nagaraj C, Nierlich P, Bálint 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Presence of Post-reperfusion pulmonary injury.	Chest tomography will be performed using 35 mA, 100 Kv and 6 mm cuts, then the simple thorax (low dose) holding the inspiration in the cephalocaudal direction with 80 mA, 100 Kv, a duration of 2.24 seconds, pitch of 1 and cuts 1 mm Multiplanar reconstructions with Kernel filters B26f, B50f and B70f for mediastinum and lung respectively, at 1 mm cuts. And anteroposterior chest radiographs will be obtained with the same equipment, at the beginning of the study and daily on days 1 to 3.	72 hours
Secondary	Concentration of cytokines (pg/ml)	Blood samples for the determination of plasma cytokines will be extracted from the peripheral venous puncture, jugular venous line and / or Swan Ganz catheter in patients undergoing EAP or by pigtail pulmonary artery trunk catheter to patients who are underwent BPA, at the following time points: baseline upon admission to hospital and / or after induction of anesthesia and before the incision (T1), and at 72 hours (T2) after the onset of surgery. All blood samples will receive the same process. immunohistochemistry will be performed for IP-10 (1: 250, ab9807; Abcam, Cambridge, UK), IL-8 (1: 100; ab7747; Abcam), MCP-1 (1: 100, ab73680; Abcam) and IL-6 (1: 100, ab6672; Abcam) will be performed with a 3,39-diaminobenzidine peroxidase substrate from R&D kit Systems (Minneapolis, MN, USA). Specifically for IP-10, IL-8, RANTES, MIG and MCP-1 will be measured by Human Chemokine Kit Cytometric Bead Array (Becton Dickinson, Franklin Lakes, NJ, USA), following the manufacturer's specifications.	Basal and at 72 hours
Secondary	Percentaje of Complications (%)	Dead	30 days