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HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.
“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.
When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.
“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.
The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.
“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.
“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.
An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.
This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.
MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.
The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).
MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
The MISTIE III results showed that this approach to clot lysis is safe and feasible for surgeons to perform even if they have had limited experience with the procedure. I think that based on these findings, minimally-invasive clot lysis will become widely adopted. It’s pretty simple to perform in most patients. At my center in Houston, we already use it on a routine basis in patients like those enrolled in MISTIE III.
Some people may focus on the neutral primary endpoint result from the MISTIE III trial, but the study made two very important findings. First, the results showed that we have improved medical management of patients who have an intracerebral hemorrhage. The 1-year functional outcomes of patients in the control group of the study who had a 41% rate of scoring 0-3 on the modified Rankin Scale after 1 year was much better than we have seen in these patients in the past. Second, the results gave a clear signal that the more clot an operator can lyse to get the residual clot to 15 mL or less, the better patients do. Faster clot lysis might also be important.
It’s hard to call the minimally-invasive approach used in MISTIE III the new standard-of-care approach for these patients given the neutral primary endpoint of the study. On the other hand, if you have a treatment that poses little risk to patients and that you know could benefit them if it succeeds in minimizing residual clot volume, then it makes sense to try it. It’s a low-risk treatment with reasonable potential for benefit. Its demonstrated safety is very important.
Louise D. McCullough, MD, PhD , is a professor of neurology and chair of neurology at the University of Texas, Houston. She had no disclosures. She made these comments in an interview.
The MISTIE III results showed that this approach to clot lysis is safe and feasible for surgeons to perform even if they have had limited experience with the procedure. I think that based on these findings, minimally-invasive clot lysis will become widely adopted. It’s pretty simple to perform in most patients. At my center in Houston, we already use it on a routine basis in patients like those enrolled in MISTIE III.
Some people may focus on the neutral primary endpoint result from the MISTIE III trial, but the study made two very important findings. First, the results showed that we have improved medical management of patients who have an intracerebral hemorrhage. The 1-year functional outcomes of patients in the control group of the study who had a 41% rate of scoring 0-3 on the modified Rankin Scale after 1 year was much better than we have seen in these patients in the past. Second, the results gave a clear signal that the more clot an operator can lyse to get the residual clot to 15 mL or less, the better patients do. Faster clot lysis might also be important.
It’s hard to call the minimally-invasive approach used in MISTIE III the new standard-of-care approach for these patients given the neutral primary endpoint of the study. On the other hand, if you have a treatment that poses little risk to patients and that you know could benefit them if it succeeds in minimizing residual clot volume, then it makes sense to try it. It’s a low-risk treatment with reasonable potential for benefit. Its demonstrated safety is very important.
Louise D. McCullough, MD, PhD , is a professor of neurology and chair of neurology at the University of Texas, Houston. She had no disclosures. She made these comments in an interview.
The MISTIE III results showed that this approach to clot lysis is safe and feasible for surgeons to perform even if they have had limited experience with the procedure. I think that based on these findings, minimally-invasive clot lysis will become widely adopted. It’s pretty simple to perform in most patients. At my center in Houston, we already use it on a routine basis in patients like those enrolled in MISTIE III.
Some people may focus on the neutral primary endpoint result from the MISTIE III trial, but the study made two very important findings. First, the results showed that we have improved medical management of patients who have an intracerebral hemorrhage. The 1-year functional outcomes of patients in the control group of the study who had a 41% rate of scoring 0-3 on the modified Rankin Scale after 1 year was much better than we have seen in these patients in the past. Second, the results gave a clear signal that the more clot an operator can lyse to get the residual clot to 15 mL or less, the better patients do. Faster clot lysis might also be important.
It’s hard to call the minimally-invasive approach used in MISTIE III the new standard-of-care approach for these patients given the neutral primary endpoint of the study. On the other hand, if you have a treatment that poses little risk to patients and that you know could benefit them if it succeeds in minimizing residual clot volume, then it makes sense to try it. It’s a low-risk treatment with reasonable potential for benefit. Its demonstrated safety is very important.
Louise D. McCullough, MD, PhD , is a professor of neurology and chair of neurology at the University of Texas, Houston. She had no disclosures. She made these comments in an interview.
HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.
“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.
When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.
“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.
The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.
“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.
“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.
An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.
This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.
MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.
The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).
MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.
“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.
When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.
“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.
The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.
“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.
“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.
An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.
This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.
MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.
The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).
MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
REPORTING FROM ISC 2019
Key clinical point: Minimally-invasive intracerebral clot lysis was safe and often effective when the residual clot shrank to 15 mL or less.
Major finding: One year after entry, 45% of MISTIE-treated patients and 41% of controls had a modified Rankin Scale score of 0-3.
Study details: MISTIE III, a multicenter, international, randomized trial of 499 patients.
Disclosures: MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.
Source: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.
