Acute Ischemic StrokePhase 2NCT04918719
Intravenous N-Acetylcysteine for the Treatment of Acute Ischemic Stroke
A Phase 2 study testing Acetylcysteine and Dextrose in Water in people with Acute Ischemic Stroke, run by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center at 1 site in United States.
Trial summary
Stroke is a major cause of death and long-term disability in the developed world. While t-PA and mechanical thrombectomy have been shown to decrease disability in properly selected patients, many patients are left with lifelong symptoms. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Ischemic Stroke
- What is being tested?
- Acetylcysteine and Dextrose in Water
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Nov 2023to 17 Sep 2024
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Consecutive subjects between ages 18 years or older evaluated in the emergency department at Harbor-UCLA Medical Center with signs and symptoms of acute ischemic stroke presenting within 24 hours of symptom onset. All individuals regardless of gender or race, who have an NIHSS of at least 5 will be eligible for this study to be included. For adults who cannot consent for themselves because of the severity of their stroke, one of the investigators will offer participation in the study to the family member who possesses the authority for medical decision making for the patient. There is no financial incentive for either the patient or the investigator. It will also be explained that the potential benefit of giving N-acetylcysteine is unknown and that the patient will receive excellent care (standard for their presentation) whether they participate or not and outside of not receiving the study drug.
- Our patients tend to be economically disadvantaged but since there are no financial incentives either for the patient or for the investigators, this bias has been minimized. Patients will receive the same care whether they participate in the study or decline.
Who cannot join
- Evidence of hemorrhagic stroke on initial CT scan
- Need for thrombectomy as determined by the treating neurologist -Known allergy to NAC
- Protected populations, including age < 18, known pregnancy, and prisoners
- Patients who are DNR/DNI at the time of presentation with a short life expectancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Harbor-UCLA Medical Center
Torrance, California, 90502
About this study
Official title: Randomized Placebo Controlled Trial of Intravenous N-Acetylcysteine for the Treatment of Acute Ischemic Stroke
Stroke is a major cause of death and long-term disability in the developed world. While t-PA and mechanical thrombectomy have been shown to decrease disability in properly selected patients, many patients are left with lifelong symptoms. There are currently limited options available for patients who are not candidates for treatment with t-PA and/or mechanical thrombectomy.
N-Acetylcysteine (NAC) is an FDA approved antioxidant and anti-inflammatory agent that has been used safely for many years in the treatment of acetaminophen overdose. In studies, the oral form has been shown to improve outcomes in acute ischemic stroke and has been shown to decrease the effects of ischemic brain injury in animal models. In a small human trial, it improved outcomes in patients suffering from mild traumatic brain injury (TBI). The intravenous formulation has a long safety record. It is not FDA approved for treating stroke but was reviewed by the FDA and was given an FDA IND for this study.
Read more
The investigators propose a prospective randomized, double-blind, placebo-controlled study to evaluate the efficacy of administering intravenous N-acetylcysteine to patients with acute ischemic stroke. Eligible subjects will receive a commercially available form of intravenous NAC (Acetadote®) through for the first 20 hours following their enrollment. Patients enrolled who receive t-PA for thrombolysis will have their intravenous NAC infusion delayed for 24 hours after the completion of their t-PA infusion. Patients undergoing thrombectomy will be excluded from enrollment. Subjects will be evaluated by emergency department and/or division of neurology physicians at the time of enrollment, during their hospitalization, as well as 30 days and 90 days after enrollment. At each visit, subjects will be assessed for functional status and quality of life.
This study is designed to compare the efficacy of intravenous N-acetylcysteine compared to normal treatment in patients with acute ischemic stroke.
Read the detailed description
Stroke is a leading cause of death and long-term disability in the United States, affecting more than 795,000 individuals annually. Of these, about 87% are ischemic strokes. In properly selected patients, intravenous recombinant tissue plasminogen activator (t-PA) has been shown to improve functional outcomes if given within 4.5 hours of the onset of stroke symptoms. Endovascular treatment both via clot retrieval devices and catheter directed t-PA has demonstrated benefit in well-selected patients with a large vessel occlusion and significant salvable tissue, also known as the penumbra. For patients who are not candidates for treatment with t-PA or mechanical thrombectomy, current treatment is centered on supportive care.
N-Acetylcysteine (NAC) is an FDA approved medication that has been used successfully for many years in the treatment of acute acetaminophen overdose. It is generally well tolerated with the exception of rare anaphylactoid type reactions to the intravenous formulation. In mouse studies, N-acetylcysteine (NAC) has led to an increase in glutathione levels in the neurons along with a reduced number of microbleeds in ischemic models. NAC treated rats have been demonstrated to have increased level of glutathione in the astrocytes which provides a neuroprotective effect. This reduced the number of microbleeds and prevented further thrombosis or infarct . The efficacy of NAC by scavenging of ROS and increasing mitochondrial activities has been shown to reduce noise-induced hearing loss in chinchilla models. Another study on transient cerebral ischemia rat models defined a new pharmacokinetic in which the neuroprotective effects of NAC are mediated by the increased protein levels of hypoxia-induced factor 1 (HIF-1), its target erythropoietin (EPO) and glucose transporter (GLUT-3).
Studies have shown consistent, similar results for ischemic brain injury in rat. Consistent human studies showing neuroprotective effects which lead to reduced symptoms after traumatic brain injury, reduced noise-induced hearing loss and as a treatment for Parkinson's disease. NAC has been shown to stimulate mitochondrial Complex 1 and 4 activities in vivo and in vitro in pre-synaptic terminals. The antioxidant effect of NAC by scavenging of ROS may prevent intracellular damage by inhibiting NF-kappaB, TNFalpha and Na+, K+ -ATPase inhibition of the neurons. In a human study of NAC for Parkinson's disease, NAC was found to mitigate the effects of ischemic brain injury in animal models. The antioxidant effect from repletion of intracellular glutathione is thought to preserve mitochondrial function and decrease cellular apoptosis. A placebo-controlled human trial demonstrated that NAC is able to decrease the effects of mild traumatic brain injury 7 days after blast injury. A recent study has shown that sufficient plasma and CSF levels can be achieved at well tolerated doses: 7 mg/kg, 35 mg/kg and 50 mg/kg.
A recent randomized placebo-controlled trial demonstrated improvement in patients given oral N-acetylcysteine every four hours for a total of 72 hours after enrollment in their NIH stroke scale and modified Rankin Score at 90 days. Intravenous N-Acetylcysteine given over 20 hours has proven to be equally efficacious in the treatment of acetaminophen toxicity and is currently the standard of care for that indication. The investigators aim to determine if intravenous NAC completed over a 20-hour course will improve NIH Stroke Scale and modified Rankin scores at 90 days. of NAC following an acute ischemic stroke.
- Conditions
- Acute Ischemic Stroke
- Being tested
- Acetylcysteine, Dextrose in Water
- Keywords
- non-hemorrhagic
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetylcysteineDrug
Also called N-acetylcysteine
The dosing of Acetylcysteine will be similar to the standard intravenous acetaminophen toxicity dosing: 200mg/kg in 1 liter of 5% Dextrose (D5W) infused over 4 hour, then 100mg/kg in 1000 milliliters D5W infused over 16 hours (Any patient receiving t-PA who enrolls in the study will have their study drug infusion delayed by 24 hours after the completion of the t-PA infusion. )
Dextrose in WaterDrug
Also called D5W, 5% Dextrose in Water
The placebo will consist of a 5% Dextrose in Water instead of NAC (dosage and timigs are the same as the NAC arm). (Any patient receiving t-PA who enrolls in the study will have their study drug infusion delayed by 24 hours after the completion of the t-PA infusion. )
| Study group | Role | What they receive |
|---|---|---|
| NAC arm | Experimental | Both arms are subjects who present with neurological deficits consistent with stroke without hemorrhage less than 24 hours since symptom onset. Both arms will receive standard of care with the study intervention being considered an "add-on" therapy. Thirty minutes after enrollment, eligible subjects will be randomized into one of two arms: placebo or N-Acetylcysteine (NAC). Any patient receiving t-PA who enrolls in the study will have their study drug infusion delayed by 24 hours after the completion of the t-PA infusion.
The dosing of NAC will be similar to the standard intravenous acetaminophen toxicity dosing: 200mg/kg in 1 liter of 5% Dextrose (D5W) infused over 4 hour, then 100mg/kg in 1000 milliliters D5W infused over 16 hours Receives: Drug: Acetylcysteine |
| Placebo arm | Placebo comparator | Both arms are subjects who present with neurological deficits consistent with stroke without hemorrhage less than 24 hours since symptom onset. Both arms will receive standard of care with the study intervention being considered an "add-on" therapy. Thirty minutes after enrollment, eligible subjects will be randomized into one of two arms: placebo or N-Acetylcysteine(NAC). Any patient receiving t-PA who enrolls in the study will have their study drug infusion delayed by 24 hours after the completion of the t-PA infusion.
The placebo will consist of a 5% Dextrose in Water (D5W) instead of NAC (dosage and timings are the same as the NAC arm). Receives: Drug: Dextrose in Water |
What is being measured
The primary outcome is the main question the study is designed to answer.
National Institutes of Health Stroke Scale (NIHSS)
The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. The single patient assessment requires less than 10 minutes to complete. The evaluation of stroke severity depends upon the ability of the observer to accurately and consistently assess the patient.
Measured: From the time of enrollment until 90 days (looking at change in NIHSS)
Secondary outcomes (5)
Modified Rankin Scale for Neurologic Disability(MRS)
The Modified Rankin Score (mRS) is a 6 point disability scale with possible scores ranging from 0 to 5. A separate category of 6 is usually added for patients who expire. The Modified Rankin Score (mRS) is the most widely used outcome measure in stroke clinical trials. Standardized interviews to obtain a mRS score are recommended at 3 months (90 days) following hospital discharge.
Measured: Obtained at 90 days
Glascow Outcome Scale (GOS)
The Glasgow Outcome Score applies to patients with brain damage allowing the objective assessment of their recovery in five categories. This allows a prediction of the long-term course of rehabilitation to return to work and everyday life.
- Death Severe injury or death without recovery of consciousness
- Persistent vegetative state Severe damage with prolonged state of unresponsiveness and a lack of higher mental functions
- Severe disability Severe injury with permanent need for help with daily living
- Moderate disability No need for assistance in everyday life, employment is possible but may require special equipment.
- Low disability Light damage with minor neurological and psychological deficits.
Measured: Obtained at 90 days
Barthel Index (BI)
The Barthel index is an ordinal scale that measures functional independence in the domains of personal care and mobility in patients with chronic, disabling conditions, especially in the rehabilitation settings.
Measured: Obtained at 90 days
Neuronal specific enolase blood level
Neuronal specific enolase levels obtained at enrollment at at 90 days
Measured: From the time of enrollment and at 90 days
MRI
Volumetric measure the extent of stroke will be quantitated
Measured: Comparison of the volume of stroke noted on initial MRI will be compared to MRI at 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2021
- Study start2 Nov 2023
- Primary completion17 Sep 2024
- Study completion17 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (35)Papers the sponsor has linked to this study.
- Other trials for Acute Ischemic StrokeStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized double blinded clinical trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David Tanen, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Investigators
- David Tanen, MD, Principal investigator, Lundquist LABiomed
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04918719
- Sponsor's protocol ID
- 32358-01
- Status last verified
- Feb 2026
- First submitted
- 27 May 2021
- Last updated
- 19 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Mussolino ME, Neumar RW, Nichol G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation. 2014 Jan 21;129(3):e28-e292. doi: 10.1161/01.cir.0000441139.02102.80. Epub 2013 Dec 18. No abstract available.
PubMed 24352519National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995 Dec 14;333(24):1581-7. doi: 10.1056/NEJM199512143332401.
PubMed 7477192Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D; ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008 Sep 25;359(13):1317-29. doi: 10.1056/NEJMoa0804656.
PubMed 18815396Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM; EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015 Mar 12;372(11):1009-18. doi: 10.1056/NEJMoa1414792. Epub 2015 Feb 11.
PubMed 25671797Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD; ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015 Mar 12;372(11):1019-30. doi: 10.1056/NEJMoa1414905. Epub 2015 Feb 11.
PubMed 25671798Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du Mesnil de Rochemont R, Singer OC, Jahan R; SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015 Jun 11;372(24):2285-95. doi: 10.1056/NEJMoa1415061. Epub 2015 Apr 17.
PubMed 25882376Prescott LF, Park J, Ballantyne A, Adriaenssens P, Proudfoot AT. Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet. 1977 Aug 27;2(8035):432-4. doi: 10.1016/s0140-6736(77)90612-2.
PubMed 70646Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med. 1988 Dec 15;319(24):1557-62. doi: 10.1056/NEJM198812153192401.
PubMed 3059186Prescott LF, Illingworth RN, Critchley JA, Stewart MJ, Adam RD, Proudfoot AT. Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning. Br Med J. 1979 Nov 3;2(6198):1097-100. doi: 10.1136/bmj.2.6198.1097.
PubMed 519312Kao LW, Kirk MA, Furbee RB, Mehta NH, Skinner JR, Brizendine EJ. What is the rate of adverse events after oral N-acetylcysteine administered by the intravenous route to patients with suspected acetaminophen poisoning? Ann Emerg Med. 2003 Dec;42(6):741-50. doi: 10.1016/s0196-0644(03)00508-0.
PubMed 14634597Yip L, Dart RC, Hurlbut KM. Intravenous administration of oral N-acetylcysteine. Crit Care Med. 1998 Jan;26(1):40-3. doi: 10.1097/00003246-199801000-00014.
PubMed 9428541Bueche CZ, Garz C, Kropf S, Bittner D, Li W, Goertler M, Heinze HJ, Reymann K, Braun H, Schreiber S. NAC changes the course of cerebral small vessel disease in SHRSP and reveals new insights for the meaning of stases - a randomized controlled study. Exp Transl Stroke Med. 2013 Apr 15;5:5. doi: 10.1186/2040-7378-5-5. eCollection 2013.
PubMed 23587288Kopke RD, Weisskopf PA, Boone JL, Jackson RL, Wester DC, Hoffer ME, Lambert DC, Charon CC, Ding DL, McBride D. Reduction of noise-induced hearing loss using L-NAC and salicylate in the chinchilla. Hear Res. 2000 Nov;149(1-2):138-46. doi: 10.1016/s0378-5955(00)00176-3.
PubMed 11033253Zhang Z, Yan J, Taheri S, Liu KJ, Shi H. Hypoxia-inducible factor 1 contributes to N-acetylcysteine's protection in stroke. Free Radic Biol Med. 2014 Mar;68:8-21. doi: 10.1016/j.freeradbiomed.2013.11.007. Epub 2013 Dec 1.
PubMed 24296245Cuzzocrea S, Mazzon E, Costantino G, Serraino I, Dugo L, Calabro G, Cucinotta G, De Sarro A, Caputi AP. Beneficial effects of n-acetylcysteine on ischaemic brain injury. Br J Pharmacol. 2000 Jul;130(6):1219-26. doi: 10.1038/sj.bjp.0703421.
PubMed 10903958
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Placebo Controlled Trial of Intravenous N-Acetylcysteine for the Treatment of Acute Ischemic Stroke
- ClinicalTrials.gov ID
- NCT04918719
- Acronym / sponsor ID
- 32358-01
- Conditions
- Acute Ischemic Stroke
- Keywords
- non-hemorrhagic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterUniversity, hospital or other
- Study start
- 2 Nov 2023 (actual)
- Primary completion
- 17 Sep 2024 (actual)
- Study completion
- 17 Sep 2024 (actual)
- First posted
- 9 Jun 2021 (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.
Stroke is a major cause of death and long-term disability in the developed world. While t-PA and mechanical thrombectomy have been shown to decrease disability in properly selected patients, many patients are left with lifelong symptoms. There are currently limited options available for patients who are not candidates for treatment with t-PA and/or mechanical thrombectomy.
N-Acetylcysteine (NAC) is an FDA approved antioxidant and anti-inflammatory agent that has been used safely for many years in the treatment of acetaminophen overdose. In studies, the oral form has been shown to improve outcomes in acute ischemic stroke and has been shown to decrease the effects of ischemic brain injury in animal models. In a small human trial, it improved outcomes in patients suffering from mild traumatic brain injury (TBI). The intravenous formulation has a long safety record. It is not FDA approved for treating stroke but was reviewed by the FDA and was given an FDA IND for this study.
The investigators propose a prospective randomized, double-blind, placebo-controlled study to evaluate the efficacy of administering intravenous N-acetylcysteine to patients with acute ischemic stroke. Eligible subjects will receive a commercially available form of intravenous NAC (Acetadote®) through for the first 20 hours following their enrollment. Patients enrolled who receive t-PA for thrombolysis will have their intravenous NAC infusion delayed for 24 hours after the completion of their t-PA infusion. Patients undergoing thrombectomy will be excluded from enrollment. Subjects will be evaluated by emergency department and/or division of neurology physicians at the time of enrollment, during their hospitalization, as well as 30 days and 90 days after enrollment. At each visit, subjects will be assessed for functional status and quality of life.
This study is designed to compare the efficacy of intravenous N-acetylcysteine compared to normal treatment in patients with acute ischemic stroke.
Detailed description
Stroke is a leading cause of death and long-term disability in the United States, affecting more than 795,000 individuals annually. Of these, about 87% are ischemic strokes. In properly selected patients, intravenous recombinant tissue plasminogen activator (t-PA) has been shown to improve functional outcomes if given within 4.5 hours of the onset of stroke symptoms. Endovascular treatment both via clot retrieval devices and catheter directed t-PA has demonstrated benefit in well-selected patients with a large vessel occlusion and significant salvable tissue, also known as the penumbra. For patients who are not candidates for treatment with t-PA or mechanical thrombectomy, current treatment is centered on supportive care.
N-Acetylcysteine (NAC) is an FDA approved medication that has been used successfully for many years in the treatment of acute acetaminophen overdose. It is generally well tolerated with the exception of rare anaphylactoid type reactions to the intravenous formulation. In mouse studies, N-acetylcysteine (NAC) has led to an increase in glutathione levels in the neurons along with a reduced number of microbleeds in ischemic models. NAC treated rats have been demonstrated to have increased level of glutathione in the astrocytes which provides a neuroprotective effect. This reduced the number of microbleeds and prevented further thrombosis or infarct . The efficacy of NAC by scavenging of ROS and increasing mitochondrial activities has been shown to reduce noise-induced hearing loss in chinchilla models. Another study on transient cerebral ischemia rat models defined a new pharmacokinetic in which the neuroprotective effects of NAC are mediated by the increased protein levels of hypoxia-induced factor 1 (HIF-1), its target erythropoietin (EPO) and glucose transporter (GLUT-3).
Studies have shown consistent, similar results for ischemic brain injury in rat. Consistent human studies showing neuroprotective effects which lead to reduced symptoms after traumatic brain injury, reduced noise-induced hearing loss and as a treatment for Parkinson's disease. NAC has been shown to stimulate mitochondrial Complex 1 and 4 activities in vivo and in vitro in pre-synaptic terminals. The antioxidant effect of NAC by scavenging of ROS may prevent intracellular damage by inhibiting NF-kappaB, TNFalpha and Na+, K+ -ATPase inhibition of the neurons. In a human study of NAC for Parkinson's disease, NAC was found to mitigate the effects of ischemic brain injury in animal models. The antioxidant effect from repletion of intracellular glutathione is thought to preserve mitochondrial function and decrease cellular apoptosis. A placebo-controlled human trial demonstrated that NAC is able to decrease the effects of mild traumatic brain injury 7 days after blast injury. A recent study has shown that sufficient plasma and CSF levels can be achieved at well tolerated doses: 7 mg/kg, 35 mg/kg and 50 mg/kg.
A recent randomized placebo-controlled trial demonstrated improvement in patients given oral N-acetylcysteine every four hours for a total of 72 hours after enrollment in their NIH stroke scale and modified Rankin Score at 90 days. Intravenous N-Acetylcysteine given over 20 hours has proven to be equally efficacious in the treatment of acetaminophen toxicity and is currently the standard of care for that indication. The investigators aim to determine if intravenous NAC completed over a 20-hour course will improve NIH Stroke Scale and modified Rankin scores at 90 days. of NAC following an acute ischemic stroke.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized double blinded clinical trial
| Arm | Type | Receives |
|---|---|---|
| NAC arm | Experimental | Drug: AcetylcysteineBoth arms are subjects who present with neurological deficits consistent with stroke without hemorrhage less than 24 hours since symptom onset. Both arms will receive standard of care with the study intervention being considered an "add-on" therapy. Thirty minutes after enrollment, eligible subjects will be randomized into one of two arms: placebo or N-Acetylcysteine (NAC). Any patient receiving t-PA who enrolls in the study will have their study drug infusion delayed by 24 hours after the completion of the t-PA infusion. The dosing of NAC will be similar to the standard intravenous acetaminophen toxicity dosing: 200mg/kg in 1 liter of 5% Dextrose (D5W) infused over 4 hour, then 100mg/kg in 1000 milliliters D5W infused over 16 hours |
| Placebo arm | Placebo comparator | Drug: Dextrose in WaterBoth arms are subjects who present with neurological deficits consistent with stroke without hemorrhage less than 24 hours since symptom onset. Both arms will receive standard of care with the study intervention being considered an "add-on" therapy. Thirty minutes after enrollment, eligible subjects will be randomized into one of two arms: placebo or N-Acetylcysteine(NAC). Any patient receiving t-PA who enrolls in the study will have their study drug infusion delayed by 24 hours after the completion of the t-PA infusion. The placebo will consist of a 5% Dextrose in Water (D5W) instead of NAC (dosage and timings are the same as the NAC arm). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Consecutive subjects between ages 18 years or older evaluated in the emergency department at Harbor-UCLA Medical Center with signs and symptoms of acute ischemic stroke presenting within 24 hours of symptom onset. All individuals regardless of gender or race, who have an NIHSS of at least 5 will be eligible for this study to be included. For adults who cannot consent for themselves because of the severity of their stroke, one of the investigators will offer participation in the study to the family member who possesses the authority for medical decision making for the patient. There is no financial incentive for either the patient or the investigator. It will also be explained that the potential benefit of giving N-acetylcysteine is unknown and that the patient will receive excellent care (standard for their presentation) whether they participate or not and outside of not receiving the study drug.
- Our patients tend to be economically disadvantaged but since there are no financial incentives either for the patient or for the investigators, this bias has been minimized. Patients will receive the same care whether they participate in the study or decline.
Key exclusion criteria (4 listed)
- Evidence of hemorrhagic stroke on initial CT scan
- Need for thrombectomy as determined by the treating neurologist -Known allergy to NAC
- Protected populations, including age < 18, known pregnancy, and prisoners
- Patients who are DNR/DNI at the time of presentation with a short life expectancy
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 |
|---|---|---|
| AcetylcysteineAlso: N-acetylcysteineThe dosing of Acetylcysteine will be similar to the standard intravenous acetaminophen toxicity dosing: 200mg/kg in 1 liter of 5% Dextrose (D5W) infused over 4 hour, then 100mg/kg in 1000 milliliters D5W infused over 16 hours (Any patient receiving t-PA who enrolls in the study will have their study drug infusion delayed by 24 hours after the completion of the t-PA infusion. ) | Drug | NAC arm |
| Dextrose in WaterAlso: D5W, 5% Dextrose in WaterThe placebo will consist of a 5% Dextrose in Water instead of NAC (dosage and timigs are the same as the NAC arm). (Any patient receiving t-PA who enrolls in the study will have their study drug infusion delayed by 24 hours after the completion of the t-PA infusion. ) | Drug | Placebo arm |
Primary outcome
National Institutes of Health Stroke Scale (NIHSS)
Time frame: From the time of enrollment until 90 days (looking at change in NIHSS)
The NIHSS is a 15-item neurologic examination stroke scale used to evaluate the effect of acute cerebral infarction on the levels of consciousness, language, neglect, visual-field loss, extraocular movement, motor strength, ataxia, dysarthria, and sensory loss. A trained observer rates the patent's ability to answer questions and perform activities. Ratings for each item are scored with 3 to 5 grades with 0 as normal, and there is an allowance for untestable items. The single patient assessment requires less than 10 minutes to complete. The evaluation of stroke severity depends upon the ability of the observer to accurately and consistently assess the patient.
5 secondary outcomes
Modified Rankin Scale for Neurologic Disability(MRS)
Time frame: Obtained at 90 days
Glascow Outcome Scale (GOS)
Time frame: Obtained at 90 days
Barthel Index (BI)
Time frame: Obtained at 90 days
Neuronal specific enolase blood level
Time frame: From the time of enrollment and at 90 days
MRI
Time frame: Comparison of the volume of stroke noted on initial MRI will be compared to MRI at 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2026.
- Background: PubMed 24352519Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Mussolino ME, Neumar RW, Nichol G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation. 2014 Jan 21;129(3):e28-e292. doi: 10.1161/01.cir.0000441139.02102.80. Epub 2013 Dec 18. No abstract available.
- Background: PubMed 7477192National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995 Dec 14;333(24):1581-7. doi: 10.1056/NEJM199512143332401.
- Background: PubMed 18815396Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, Larrue V, Lees KR, Medeghri Z, Machnig T, Schneider D, von Kummer R, Wahlgren N, Toni D; ECASS Investigators. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008 Sep 25;359(13):1317-29. doi: 10.1056/NEJMoa0804656.
- Background: PubMed 25671797Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM; EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015 Mar 12;372(11):1009-18. doi: 10.1056/NEJMoa1414792. Epub 2015 Feb 11.
- Background: PubMed 25671798Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD; ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015 Mar 12;372(11):1019-30. doi: 10.1056/NEJMoa1414905. Epub 2015 Feb 11.
- Background: PubMed 25882376Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du Mesnil de Rochemont R, Singer OC, Jahan R; SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015 Jun 11;372(24):2285-95. doi: 10.1056/NEJMoa1415061. Epub 2015 Apr 17.
- Background: PubMed 70646Prescott LF, Park J, Ballantyne A, Adriaenssens P, Proudfoot AT. Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine. Lancet. 1977 Aug 27;2(8035):432-4. doi: 10.1016/s0140-6736(77)90612-2.
- Background: PubMed 3059186Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med. 1988 Dec 15;319(24):1557-62. doi: 10.1056/NEJM198812153192401.
- Background: PubMed 519312Prescott LF, Illingworth RN, Critchley JA, Stewart MJ, Adam RD, Proudfoot AT. Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning. Br Med J. 1979 Nov 3;2(6198):1097-100. doi: 10.1136/bmj.2.6198.1097.
- Background: PubMed 14634597Kao LW, Kirk MA, Furbee RB, Mehta NH, Skinner JR, Brizendine EJ. What is the rate of adverse events after oral N-acetylcysteine administered by the intravenous route to patients with suspected acetaminophen poisoning? Ann Emerg Med. 2003 Dec;42(6):741-50. doi: 10.1016/s0196-0644(03)00508-0.
- Background: PubMed 9428541Yip L, Dart RC, Hurlbut KM. Intravenous administration of oral N-acetylcysteine. Crit Care Med. 1998 Jan;26(1):40-3. doi: 10.1097/00003246-199801000-00014.
- Background: PubMed 23587288Bueche CZ, Garz C, Kropf S, Bittner D, Li W, Goertler M, Heinze HJ, Reymann K, Braun H, Schreiber S. NAC changes the course of cerebral small vessel disease in SHRSP and reveals new insights for the meaning of stases - a randomized controlled study. Exp Transl Stroke Med. 2013 Apr 15;5:5. doi: 10.1186/2040-7378-5-5. eCollection 2013.
- Foundation NS. Clinical Guidelines For Stroke Management. Melbourne Australia2010.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
David Tanen, MD principal investigator
Lundquist LABiomed
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acetylcysteine and Dextrose in Water in people with Acute Ischemic Stroke, run by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center at 1 site in United States.
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 2 inclusion and 4 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: finished, as of the sponsor's last update on 19 Feb 2026. 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 United States. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
National Institutes of Health Stroke Scale (NIHSS) (time frame: From the time of enrollment until 90 days (looking at change in NIHSS)). 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 NCT04918719, which also lists 35 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 19 Feb 2026.