- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04081012
N-acetyl Cysteine in Post-reperfusion Pulmonary Injury in Chronic Thromboembolic Pulmonary Hypertension. (NAC-PostRep)
N-acetyl Cysteine in Post-reperfusion Pulmonary Injury in Patients With Chronic Thromboembolic Pulmonary Hypertension Undergoing Pulmonary Balloon Angioplasty and Pulmonary Endarterectomy.
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Maria Elena Soto Lopez, Dr.
- Phone Number: 5538808997
- Email: mesoto50@hotmail.com
Study Contact Backup
- Name: Huitzilihuitl Saucedo Orozco, Dr.
- Phone Number: 4921373556
- Email: huitzilihuitls@hotmail.com
Study Locations
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Ciudad de mexico, Mexico, 14080
- Recruiting
- Instituto Nacional Ignacio Chavez
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Contact:
- Huitzilihuitl Saucedo Orozco, Dr.
- Phone Number: 4921373556
- Email: huitzilihuitls@hotmail.com
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Contact:
- Maria Elena Soto López, Dr.
- Phone Number: 5538880897
- Email: mesoto50@hotmail.com
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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 endarterectomy or balloon angioplasty.
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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.
Other Names:
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Placebo Comparator: Placebo
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
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The placebo group will receive a similar volume of normal saline as a placebo at the same time intervals.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Presence of Post-reperfusion pulmonary injury.
Time Frame: 72 hours
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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.
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72 hours
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Concentration of cytokines (pg/ml)
Time Frame: Basal and at 72 hours
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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.
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Basal and at 72 hours
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Percentaje of Complications (%)
Time Frame: 30 days
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Dead
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30 days
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Collaborators and Investigators
Investigators
- Principal Investigator: Maria Elena Soto Lopez, Instituto Nacional de Cardiología "Ignacio Chávez"
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Respiratory Tract Diseases
- Lung Diseases
- Wounds and Injuries
- Thoracic Injuries
- Hypertension
- Hypertension, Pulmonary
- Lung Injury
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Protective Agents
- Respiratory System Agents
- Antioxidants
- Antidotes
- Free Radical Scavengers
- Expectorants
- Acetylcysteine
- N-monoacetylcystine
Other Study ID Numbers
- 191110
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
- Clinical Study Report (CSR)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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