Condition category
Circulatory System
Date applied
05/06/2020
Date assigned
19/08/2020
Last edited
19/08/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
When brain arteries bleed abruptly into the subarachnoid space (the interval between the arachnoid membrane and the pia mater, containing cerebrospinal fluid), a subarachnoid hemorrhage has occurred. The most common cause of subarachnoid hemorrhage is the bulging of a cerebral artery wall called an aneurysm.
One of the serious complications of subarachnoid hemorrhage is the transient narrowing of the arteries (due to spasms) which is called cerebral vasospasm. Cerebral vasospasm is the main cause of mortality and morbidity following an aneurysmal subarachnoid hemorrhage. As the cerebral arteries provide glucose and oxygen for brain tissue, a reduced blood supply causes cerebral ischemia in about more than two-thirds of patients who experience aneurysmal subarachnoid hemorrhage. Also, a considerable portion of the survivors suffers neurological symptoms like paralysis, numbness, and etc.
The exact mechanisms of the cerebral vasospasm are not well understood. However, there are some pieces of evidence that demonstrate the important role of inflammation. The aim of this study is to investigate whether anti-inflammatory medications can prevent cerebral vasospasm. Evaluation of the vascular spasms will be implemented by the doppler sonography of cerebral arteries.

Who can participate?
Patients with subarachnoid hemorrhage following the rupture of a cerebral aneurysm can participate in this study.

What does the study involve?
Patients are randomly allocated into two groups. The first group will take ibuprofen and for the second group, a sham will be administered that is totally similar to the drug. Participants in both groups will take either the drug or sham for two weeks, four times a day, and both groups will receive standard treatment at the same time.

What are the possible benefits and risks of participating?
Although evidence from some in vitro and very limited human experiments are promising for the possible preventive effects of ibuprofen on cerebral vasospasm, we might not see those benefits among participants. However, it is a worthwhile opportunity to support a research that directly helps to discover possible new pathways in the prevention of cerebral vasospasm and its mishaps secondary to the complications.
Ibuprofen is a commonly used non-steroidal anti-inflammatory drug (NSAID) that may have some adverse effects such as dizziness, heartburn, nausea, rash, and tinnitus in people without comorbidities. Acute kidney injury is a rare adverse effect of these medications. The most serious adverse effects of NSAIDs are gastrointestinal (GI) bleeding and increased risk of some heart diseases. Nonetheless, the administration of anti-acid medications can significantly lower the occurrence of GI complications. Also, previous long term consumption of antiplatelet medications like aspirin is a predisposing factor for GI bleeding. Patients with existing heart disease or risk factors for such diseases may be at greater risk for heart complications. In this study, before enrollment, patients will be assessed for risk factors and will be stratified based on their chronic diseases and type of their medications to exclude those with high risk and decrease the probability of any mishap for the others as much as possible. Also, the participants are under 24-hour close observation of our clinical experts in the intensive care unit and any possible complications will be managed promptly by them based on the institutional protocols.

Where is the study run from?
The study will be conducted in Qaem teaching Hospital (Mashhad, Iran).

When is the study starting and how long is it expected to run for?
September 2018 to June 2021

Who is funding the study?
Mashhad University of Medical Sciences (MUMS).

Who is the main contact?
Dr Samira Zabihyan
zabihyan@yahoo.com

Trial website

Contact information

Type

Scientific

Primary contact

Dr Samira Zabihiyan

ORCID ID

http://orcid.org/0000-0003-0742-6664

Contact details

Department of Neurosurgery
Ghaem Teaching Hospital
Ahmad Abad Blvd
Mashhad
99199-91766
Iran
+98 (0)9151115783
Zabihyans@mums.ac.ir

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

971587

Study information

Scientific title

Prophylactic effects of ibuprofen vs placebo on cerebral vasospasm following aneurysmal subarachnoid hemorrhage: a single-center randomized, controlled pilot trial

Acronym

Study hypothesis

Ibuprofen can prevent subsequent cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

Ethics approval

Approved 09/04/2019, Mashhad University of Medical Sciences (MUMS) ethical committee (Mashhad University of Medical Sciences, Ghorashi building, Daneshgah Street, Mashhad, 91388-13944, Iran; +98 5138411538; vcresearch@mums.ac.ir), ref: IR.MUMS.MEDICAL.REC.1398.225

Study design

Single-center feasibility study for a double-blind randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Vasospasms following aneurysmal subarachnoid hemorrhage

Intervention

Eligible participants are adult patients 18 years old and older with an aneurysmal subarachnoid hemorrhage confirmed by a brain CT scan, CT angiography, magnetic resonance angiography or digital subtraction angiography who admitted to the emergency department within 6 hours of the ictus. Those who meet the inclusion criteria will be randomized based on a generated permuted block randomization table using an online random sequence generator with an allocation list in random order. The allocation ratio is 1:1. Then, an independent investigator allocates participants into two groups for the administration of either ibuprofen or placebo. The intervention group will receive Ibuprofen capsules 400 mg/every 6 hours for 14 days. Placebo is given to the control group. At the same time, both groups will concomitantly be treated by the standard of care of aSAH treatment for 2 weeks including nimodipine and phenytoin. Microsurgical aneurysmal clipping or interventional coiling will be performed for patients who have an indication based on the researchers' protocols.

Intervention type

Drug

Phase

Phase III

Drug names

Ibuprofen

Primary outcome measure

Feasibility outcomes (measured using case report forms):
1. Ability to recruit 30 participants over 12 months
2. Ability to follow 85% of participants for 3 months
3. Patient compliance with the study treatment if 75% of participants comply with 75% of the protocol

Secondary outcome measures

Outcomes for the definitive trial:
1. All-cause mortality until discharge and by the end of follow-up measured using patient records
2. Cerebral vasospasm: defined as detection of vasospasm by either digital subtraction angiography (DSA) or transcranial Doppler (TCD). Angiographic vasospasm is defined as focal or generalized reduction of cerebral arterial caliber on conventional cerebral angiogram. TCD vasospasm is defined as any peak systolic middle cerebral artery velocity (PSVMCA) _120 cm/s and a Lindegaard ratio of >3 and it will be assessed every other day during the hospitalization
3. Delayed cerebral ischemia (DCI): The occurrence of DCI defined as the development of new, focal neurological deficits, and/or a decreased level of consciousness of at least two points on the Glasgow Coma Scale (GCS) after other possible causes of deterioration have been excluded assessed every other day during the hospitalization
4. Disability at discharge and 3 months using Modified Rankin Scale (mRS) at three-month follow-up. Favorable mRS outcomes are (mRS 1 and 2) and unfavorable outcomes are (mRS 3 to 6)

Overall trial start date

08/09/2018

Overall trial end date

01/06/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Aneurysmal subarachnoid hemorrhage verified by a brain CT scan
2. Older than 18 years old
3. Admitted less than 6 hours after the onset of clinical symptoms
4. World Federation of Neurological Surgeons (WFNS) score I, II and III at admission

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

There are 30 participants in this study

Participant exclusion criteria

1. Patients who have hypersensitivity to aspirin, ibuprofen or other NSAIDs
2. Previous and prolonged use of any type of NSAIDs other than aspirin
3. History of aneurysmal re-bleeding, and active bleeding of a gastrointestinal ulcer, hemodynamic instability, and pregnancy
4. Patients with a history of myocardial infarction(MI) or percutaneous coronary interventions

Recruitment start date

01/09/2020

Recruitment end date

01/01/2021

Locations

Countries of recruitment

Iran

Trial participating centre

Ghaem teaching Hospital
Ahmad Abad Blvd
Mashhad
99199-91766
Iran

Sponsor information

Organisation

Mashhad University of Medical Sciences

Sponsor details

Knowledge and Health City
Shahid Fakouri Blvd (In front of Fakouri 94)
Razavi-Khorasan province
Mashhad
91778-99191
Iran
+98 (0)51 38049
presidentoffice@mums.ac.ir

Sponsor type

University/education

Website

http://www.mums.ac.ir/

Funders

Funder type

University/education

Funder name

Mashhad University of Medical Sciences

Alternative name(s)

MUMS

Funding Body Type

government organisation

Funding Body Subtype

Local government

Location

Iran

Results and Publications

Publication and dissemination plan

It is anticipated that the results of this study will be presented in international meetings, early 2021 and the article will be published during late 2021.

IPD sharing statement:
All data generated or analysed during this study will be included in the subsequent results publication.

Intention to publish date

31/12/2021

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

19/08/2020: Trial’s existence confirmed by Mashad University of Medical Sciences