Trial document




drksid header

  DRKS00011177

Trial Description

start of 1:1-Block title

Title

Remote ischemic preconditioning in patients with aneurysmal subarachnoid hemorrhage

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

RIP_SAH

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

Aneurysmal subarachnoid hemorrhage following the rupture of an intracranial aneurysm is a severe condition accompanied by high morbidity and mortality. A large number of patients deceases or sustains severe brain damage and disability. Aside from the bleeding itself causing increased intracranial pressure and decreased cerebral blood flow, cerebral ischemia due to cerebral vasospasm is the most important complication within the first 14 days after bleeding.
Remote ischemic preconditioning (RIPC), which means induced transient episodes of ischemia by the occlusion of blood flow in non-target tissue is successful used especially in cardiac surgery to protect against ischemic injury. This study is to assess whether RIPC reduces the risk and volume on imaging of cerebral ischemia in patients after aneurysmal subarachnoid hemorrhage.
For remote ischemic preconditioning, a standard blood pressure cuff is fixed on the patient’s upper extremity. Participants in the intervention group will receive RIPC by inflating the cuff for sittings of 3 x 5 min to 200 mmHg alternating with 5 min of complete cuff deflation, with four sittings per day in the first ten days after aneurysm treatment. In the sham group, the maximum cuff pressure will be limited to 10 mmHg for 3 x 5 min alternating with 5 min of complete cuff deflation.

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

Despite both early surgical or interventional therapy and extensive treatment at the intensive care unit, aneurysmal subarachnoid hemorrhage (SAH) still is associated with high morbidity and mortality. Aside from the hemorrhage itself causing increased intracranial pressure and decreased cerebral blood flow, delayed cerebral ischemia (DCI) due to cerebral vasospasm following subarachnoid hemorrhage (SAH) is a critical complication within the first 14 days post SAH in those patients who survive the initial bleeding. Up to 30 % of patients with aneurysmal SAH are affected by DCI and most of them experience motor deficits, cognitive dysfunction and reduced quality of life. The risk of DCI, which is of a multifactorial aetiology, first and foremost depends on the severity of the initial hemorrhage and on the amount of subarachnoidal and intraventricular blood on initial imaging. For prevention of vasospasm and DCI, the current standard is to apply vasodilatative pharmacological treatment with nimodipine, which has been confirmed to improve overall outcome in SAH patients. However, the precise mechanism behind the beneficial effects of treatment with nimodipine remains unclear. Additionally, the management of vasospasm includes sustaining arterial hypertension and hypervolaemia. The historical “Triple H” therapy with added haemodilution has been largely abandoned. Furthermore, interventional therapy by ballon angioplasty or chemical vasospasmolysis by an intravasal application of nimodipine is employed in symptomatic patients. For neuromonitoring and the early detection of cerebral vasospasm, regular neurological assessment and daily transcranial doppler sonography are the most sensitive and specific instruments. Nevertheless, the incidence of vasospasm is high and still associated with severe morbidity and mortality. Novel strategies for the prevention of cerebral ischemia due to cerebral vasospasm are thus required. Ischemic preconditioning, also known as induced tolerance, was previosly described as a promising strategy for achieving neuroprotection in several studies. Remote ischemic preconditioning (RIPC) is based on inducing an ischemic stimulus either directly to the area which is at risk for DCI or in a part of the body that is remote from the target organ at risk, for example by the occlusion of blood flow in extremities. While RIPC has been established with promising results in cardiac surgery to reduce the risk of myocardial ischemia, there have been only sparse efforts made in neurosurgical appliances. In a recently published article by Sales et al., a benefit of RIPC in terms of the amount of postoperative ischemic tissue damage for patients undergoing elective brain tumor surgery was demonstrated. This is the first study indicating a benefit of RIPC in brain tumor surgery. The exact underlying pathomechanisms remain unknown, but presumably, RIPC may induce endogenous mechanisms protecting the brain against noxious stimuli and ischemia. This study is to assess whether RIPC reduces the volume of cerebral ischemia in patients after aneurysmal subarachnoid hemorrhage.

end of 1:1-Block scientific synopsis
start of 1:1-Block forwarded Data

Do you plan to share individual participant data with other researchers?

[---]*

end of 1:1-Block forwarded Data
start of 1:1-Block forwarded Data Content

Description IPD sharing plan:

[---]*

end of 1:1-Block forwarded Data Content
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00011177
  •   2019/09/09
  •   [---]*
  •   yes
  •   Approved
  •   336/16s, Ethik-Kommission der Fakultät für Medizin der Technischen Universität München
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  • [---]*
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   I60.7 -  Subarachnoid haemorrhage from intracranial artery, unspecified
  •   I63.9 -  Cerebral infarction, unspecified
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Participants will be randomised 1:1 to either the intervention (preconditioning) group or the control (sham) group. In both RIPC and SPC, a standard blood pressure cuff is
    fixed on the patient’s upper extremity. Participants in the intervention group will receive RIPC by inflating the cuff for sittings of 5 min to 200 mmHg alternating with 5 min of complete cuff deflation and again two repetitions in this manner. This is repeated for a total of four sittings per day during the in-patient stay after aneurysm treatment.
  •   In the sham group, the maximum cuff pressure will be limited to 10 mmHg for 3 x 5 min alternating with 5 min of complete cuff deflation.
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist, caregiver, assessor, data analyst
  •   Placebo
  •   Treatment
  •   Parallel
  •   N/A
  •   N/A
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

Volumetry of ischemic area con cranial CT scan 2 to 3 weeks post subarachnoid hemorrhage

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

Secondary outcome is the severity of neurological impairment, which will be scored by the National Institutes of Health Stroke Scale (NIHSS) at time at admission to the hospital, 1 and 2 weeks, 3 months and 1 year after bleeding and by the Modified Rankin Scale (mRS) at discharge, 3 months and 1 year after bleeding. Furthermore, doppler studies will be conducted daily for the detection of vasospasm.

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   Germany
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  • University Medical Center 
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   Actual
  •   2019/11/01
  •   60
  •   Monocenter trial
  •   National
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

- patients suffering from aneurysmal subarachnoidal bleeding
- written consent for study participation by patient, family member or by an independent physician in case of inability to consent
- age > 18 years

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

- peripheral arterial disease
- time after hemorrhage >48 hours
- diabetes mellitus and intake of oral antidiabetic medication
- inability to consent
- pregnancy
- age< 18 years

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar
    • Mr.  PD Dr  Jens  Gempt 
    • Ismaninger Str. 22
    • 81675  München
    • Germany
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar
    • Mr.  PD Dr  Jens  Gempt 
    • Ismaninger Str. 22
    • 81675  München
    • Germany
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar
    • Mr.  PD Dr  Jens  Gempt 
    • Ismaninger Str. 22
    • 81675  München
    • Germany
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Neurochirurgische Klinik und Poliklinik, Klinikum rechts der Isar
    • Mr.  PD Dr  Jens  Gempt 
    • Ismaninger Str. 22
    • 81675  München
    • Germany
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting ongoing
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

  •   Study Protocol
  •   1. Da Silva, I.R., et al., Hematologic counts as predictors of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. J Crit Care, 2017. 37: p. 126-129. 2. Lackner, P., et al., Cellular microparticles as a marker for cerebral vasospasm in spontaneous subarachnoid hemorrhage. Stroke, 2010. 41(10): p. 2353-7. 3. Aydin, H.E., et al., Comparison of the effects and mechanism of the Curcumin with different acting drugs in Experimental Vasospasm after Subarachnoid Hemorrhage. Turk Neurosurg, 2016. 4. Francoeur, C.L. and S.A. Mayer, Management of delayed cerebral ischemia after subarachnoid hemorrhage. Crit Care, 2016. 20(1): p. 277. 5. Schweizer, T.A., T. Al-Khindi, and R.L. Macdonald, Mini-Mental State Examination versus Montreal Cognitive Assessment: rapid assessment tools for cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. J Neurol Sci, 2012. 316(1-2): p. 137-40. 6. Petruk, K.C., et al., Nimodipine treatment in poor-grade aneurysm patients. Results of a multicenter double-blind placebo-controlled trial. J Neurosurg, 1988. 68(4): p. 505-17. 7. Rowland, M.J., et al., Delayed cerebral ischaemia after subarachnoid haemorrhage: looking beyond vasospasm. Br J Anaesth, 2012. 109(3): p. 315-29. 8. Kunze, E., et al., Value of Perfusion CT, Transcranial Doppler Sonography, and Neurological Examination to Detect Delayed Vasospasm after Aneurysmal Subarachnoid Hemorrhage. Radiol Res Pract, 2012. 2012: p. 231206. 9. Steiger, H.J. and D. Hanggi, Ischaemic preconditioning of the brain, mechanisms and applications. Acta Neurochir (Wien), 2007. 149(1): p. 1-10. 10. Narayanan, S.V., K.R. Dave, and M.A. Perez-Pinzon, Ischemic preconditioning and clinical scenarios. Curr Opin Neurol, 2013. 26(1): p. 1-7. 11. Stevens, S.L., K.B. Vartanian, and M.P. Stenzel-Poore, Reprogramming the response to stroke by preconditioning. Stroke, 2014. 45(8): p. 2527-31. 12. Murry, C.E., R.B. Jennings, and K.A. Reimer, Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation, 1986. 74(5): p. 1124-36. 13. Kirino, T., Ischemic tolerance. J Cereb Blood Flow Metab, 2002. 22(11): p. 1283-96. 14. Sales, A.H.A., et al., Impact of ischemic preconditioning on surgical treatment of brain tumors: a single-center, randomized, double-blind, controlled trial. BMC Med, 2017. 15(1): p. 137. 15. Dirnagl, U., K. Becker, and A. Meisel, Preconditioning and tolerance against cerebral ischaemia: from experimental strategies to clinical use. Lancet Neurol, 2009. 8(4): p. 398-412. 16. Molyneux, A., et al., International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomized trial. J Stroke Cerebrovasc Dis, 2002. 11(6): p. 304-14. 17. Molyneux, A.J., et al., Risk of recurrent subarachnoid haemorrhage, death, or dependence and standardised mortality ratios after clipping or coiling of an intracranial aneurysm in the International Subarachnoid Aneurysm Trial (ISAT): long-term follow-up. Lancet Neurol, 2009. 8(5): p. 427-33. 18. Meng, R., et al., Upper limb ischemic preconditioning prevents recurrent stroke in intracranial arterial stenosis. Neurology, 2012. 79(18): p. 1853-61. 19. Tulu, S., et al., Remote ischemic preconditioning in the prevention of ischemic brain damage during intracranial aneurysm treatment (RIPAT): study protocol for a randomized controlled trial. Trials, 2015. 16: p. 594. 20. Mayor, F., et al., Effects of remote ischemic preconditioning on the coagulation profile of patients with aneurysmal subarachnoid hemorrhage: a case-control study. Neurosurgery, 2013. 73(5): p. 808-15; discussion 815. 21. Hougaard, K.D., et al., Remote ischemic perconditioning as an adjunct therapy to thrombolysis in patients with acute ischemic stroke: a randomized trial. Stroke, 2014. 45(1): p. 159-67. 22. Flynn, L.M.C., et al., Alpha Calcitonin Gene-Related Peptide Increases Cerebral Vessel Diameter in Animal Models of Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis. Front Neurol, 2017. 8: p. 357. 23. Djelilovic-Vranic, J., et al., Follow-up of Vasospasm by Transcranial Doppler Sonography (TCD) in Subarachnoid Hemorrhage (SAH). Acta Inform Med, 2017. 25(1): p. 14-18. 24. Wegener, S., et al., Transient ischemic attacks before ischemic stroke: preconditioning the human brain? A multicenter magnetic resonance imaging study. Stroke, 2004. 35(3): p. 616-21. 25. Chan, M.T., et al., Effect of ischemic preconditioning on brain tissue gases and pH during temporary cerebral artery occlusion. Acta Neurochir Suppl, 2005. 95: p. 93-6.
end of 1:n-Block publications
* This entry means the parameter is not applicable or has not been set.