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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Chronic Thromboembolic Pulmonary Hypertension

Intervention / Treatment
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* Drug: N-acetyl cysteine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-acetyl Cysteine<br>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 endarterectomy or balloon angioplasty. | Drug: N-acetyl cysteine<br>* 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.<br>* Other names: NAC;|
| Placebo Comparator: Placebo<br>The placebo group will receive a similar volume of normal saline as a placebo at the same time intervals. All study medications will be prepared by the Pharmacology department, which is not involved in patient care; the name of the medication and dose of the original ampule will be erased and also an identification label will be placed with the name, registration number, bed number, date and will be indifferent for groups with the same type of ampoule, with the same type of labeling | Drug: Placebo<br>* The placebo group will receive a similar volume of normal saline as a placebo at the same time intervals.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Percentaje of Complications (%) | Dead | 30 days |