Chronic Thromboembolic Pulmonary HypertensionNAC-PostRepNCT04081012
N-acetyl Cysteine in Post-reperfusion Pulmonary Injury in Chronic Thromboembolic Pulmonary Hypertension.
A study testing N-acetyl cysteine in people with Chronic Thromboembolic Pulmonary Hypertension, run by Instituto Nacional de Cardiologia Ignacio Chavez at 1 site in Mexico.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Chronic Thromboembolic Pulmonary Hypertension
- What is being tested?
- N-acetyl cysteine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteMexico
- Study dates
- 21 May 2019to 21 May 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients who are diagnosed with group 4 pulmonary hypertension and are susceptible to pulmonary endarterectomy or balloon angioplasty in patients over 18 years.
Who cannot join
- Patients who do not accept admission to the trial.
- Presence of arterial hypotension or sepsis.
Trial locations and contacts
1 site in 1 country.
Mexico1 site, 1 recruiting
- Recruiting
Instituto Nacional Ignacio Chavez
Mexico City, 14080
Huitzilihuitl Saucedo Orozco, Dr., 4921373556, huitzilihuitls@hotmail.com
Maria Elena Soto López, Dr., 5538880897, mesoto50@hotmail.com
About this study
Official title: N-acetyl Cysteine in Post-reperfusion Pulmonary Injury in Patients With Chronic Thromboembolic Pulmonary Hypertension Undergoing Pulmonary Balloon Angioplasty and Pulmonary Endarterectomy.
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.
Read the 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.
- Being tested
- N-acetyl cysteine, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetyl cysteineDrug
Also called NAC
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.
PlaceboDrug
The placebo group will receive a similar volume of normal saline as a placebo at the same time intervals.
| Study group | Role | What they receive |
|---|---|---|
| N-acetyl Cysteine | Experimental | 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. Receives: Drug: N-acetyl cysteine |
| Placebo | Placebo comparator | 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 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 72 hours
Secondary outcomes (2)
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.
Measured: Basal and at 72 hours
Percentaje of Complications (%)
Dead
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2019
- Study start21 May 2019
- Primary completion21 May 2023 (estimated)
- Study completion21 May 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Chronic Thromboembolic Pulmonary HypertensionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Cardiologia Ignacio Chavez
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maria Elena Soto, MsC and PhD, Instituto Nacional de Cardiologia Ignacio Chavez
- Investigators
- Maria Elena Soto Lopez, Principal investigator, Instituto Nacional de Cardiología "Ignacio Chávez"
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04081012
- Sponsor's protocol ID
- 191110
- Acronym
- NAC-PostRep
- Status last verified
- Sep 2020
- First submitted
- 16 Aug 2019
- Last updated
- 22 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data for all primary and secondary outcome measures will be made available.
Publications
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.
PubMed 26916489Huisman 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.
PubMed 29770793Pengo 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.
PubMed 15163775Ogawa 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.
PubMed 29101270Wilkens 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.
PubMed 22221974Laubach VE, Sharma AK. Mechanisms of lung ischemia-reperfusion injury. Curr Opin Organ Transplant. 2016 Jun;21(3):246-52. doi: 10.1097/MOT.0000000000000304.
PubMed 26945320Zabini 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.
PubMed 25034560Sun 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.
PubMed 25386077Geudens 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.
PubMed 17644109
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- N-acetyl Cysteine in Post-reperfusion Pulmonary Injury in Patients With Chronic Thromboembolic Pulmonary Hypertension Undergoing Pulmonary Balloon Angioplasty and Pulmonary Endarterectomy.
- ClinicalTrials.gov ID
- NCT04081012
- Acronym / sponsor ID
- NAC-PostRep / 191110
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- Instituto Nacional de Cardiologia Ignacio ChavezUniversity, hospital or other
- Study start
- 21 May 2019 (actual)
- Primary completion
- 21 May 2023 (estimated)
- Study completion
- 21 May 2023 (estimated)
- First posted
- 6 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| N-acetyl Cysteine | Experimental | Drug: N-acetyl cysteinePatients 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. |
| Placebo | Placebo comparator | Drug: PlaceboThe 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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Patients who are diagnosed with group 4 pulmonary hypertension and are susceptible to pulmonary endarterectomy or balloon angioplasty in patients over 18 years.
Key exclusion criteria (2 listed)
- Patients who do not accept admission to the trial.
- Presence of arterial hypotension or sepsis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetyl cysteineAlso: NACPatients 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. | Drug | N-acetyl Cysteine |
| PlaceboThe placebo group will receive a similar volume of normal saline as a placebo at the same time intervals. | Drug | Placebo |
Primary outcome
Presence of Post-reperfusion pulmonary injury.
Time frame: 72 hours
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.
2 secondary outcomes
Concentration of cytokines (pg/ml)
Time frame: Basal and at 72 hours
Percentaje of Complications (%)
Time frame: 30 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2020.
- Background: PubMed 26916489Konstantinides 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.
- Background: PubMed 29770793Huisman 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.
- Background: PubMed 15163775Pengo 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.
- Background: PubMed 29101270Ogawa 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.
- Background: PubMed 22221974Wilkens 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.
- Background: PubMed 26945320Laubach VE, Sharma AK. Mechanisms of lung ischemia-reperfusion injury. Curr Opin Organ Transplant. 2016 Jun;21(3):246-52. doi: 10.1097/MOT.0000000000000304.
- Background: PubMed 25034560Zabini 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.
- Background: PubMed 25386077Sun 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.
- Background: PubMed 17644109Geudens 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.
- Individual participant dataSharing planned: Yes. De-identified individual participant data for all primary and secondary outcome measures will be made available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maria Elena Soto Lopez principal investigator
Instituto Nacional de Cardiología "Ignacio Chávez"
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing N-acetyl cysteine in people with Chronic Thromboembolic Pulmonary Hypertension, run by Instituto Nacional de Cardiologia Ignacio Chavez at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Maria Elena Soto Lopez, Dr. (5538808997, mesoto50@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Presence of Post-reperfusion pulmonary injury. (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04081012, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2020.