Human Albumin for Clinical Outcome in Aneurysmal Subarachnoid Hemorrhages

NCT06548477 | Recruiting DMC

• 1 other identifier: MR-01-24-229
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

Aneurysmal subarachnoid hemorrhage (aSAH) is a dreadful acute neurological condition with overwhelmingly high rate of associated morbidities and mortality. Despite leaping advancement in neurosurgical techniques and imaging modalities, there is no substantiative improvement in overall prognosis for aSAH. Cerebral vasospasm remains the predominant cause of associated morbidities. Human albumin has been used in different neurological conditions including head trauma, intracerebral hemorrhages, and ischemic strokes with favorable outcome. However, its beneficial use in aSAH has not been sufficiently explored until recently a published systematic review by our team. In view of scarcity of published data and lack of robust evidence, our group has designed for the first ever RCT to compare the use human albumin-enhanced fluid management versus standard fluid therapy with crystalloids in patients with aSAH. This single center open label, prospective, parallel group randomized control trial will be conducted at Hamad General Hospital, Doha-Qatar from August 2024 to July 2027. A sample size of 84 (42 in each arm) has been calculated to detect as sufficient to detect a clinically significant difference in modified Rankin Scale good score between two groups (human-albumin induced volume expansion therapy versus crystalloid only) for fluid management in aneurysmal subarachnoid hemorrhages patients. Primary outcome will be based on dichotomized modified Rankin scale \[(Good grades (0-2) and poor grades (3-6)\], while secondary outcome will include symptomatic vasospasm, transcranial doppler velocities, and Pulse Index Contour Cardiac Output (PiCCO) parameters. The trial aims to provide firsthand evidence on the beneficial use of human albumin to achieve optimal fluid management regime to explore its potential role to improve clinical outcome in patients with aSAH.

Conditions

Aneurysmal Subarachnoid Hemorrhage

Keywords

HASH trial, Human Albumin, Subarachnoid hemorrhage, Aneurysmal, Effectiveness, Clinical Outcome, Protocol

Outcome Measures

Primary Outcomes (1)

• Dichomatized modified Rankin Scale (mRS)

  Primary clinical outcome will be based on dichotomized modified Rankin Scale \[(Good grades (0 -2) and poor grades (3-6)\]. Primary outcome measures (values of mRS) will be compared between study arms to assess difference in the effect size of the intervention.

  Endpoints for primary outcome measures (values of mRS) will be assessed on Day-14 and at 3 month follow up.

Secondary Outcomes (1)

• Development of Symptomatic vasospasm (with/without new onset infarctions on unenhanced Computed Tomography scan, transcranial doppler velocities (daily average) and PiCCO parameters (daily average values)

  Endpoint for secondary outcome is at day-14.

Study Arms (2)

Intervention group (Albumin group)

EXPERIMENTAL

Intervention group will receive of intermittent boluses of human albumin plus standard fluid therapy (with crystalloids only) to maintain a euvolemic fluid balance.

Drug: Human albumin

Control (crystalloid group)

NO INTERVENTION

Control group will receive only standard fluid therapy with crystalloid solutions with intermittent boluses crystalloid solution to maintain euvolemic balance

Interventions

Human albumin DRUG

Patients in intervention arm will also receive intermittent boluses of 20 percent human albumin (in addition to standard fluid therapy) that will be administered with dosage regimen of 1.25gm/kg of body weight per 24 hours. The maximum total calculated dose/volume of albumin for the patient will be infused @ 34 ml/hour (over 3 hours) and will be divided in 3 boluses, spaced at 8 hours intervals. During intervention period, duration of treatment (7-day study period) will cover the peak period of cerebral vasospasm from day 4th until 10th day. Albumin administration will be tailored according to the targeted values set for euvolemic fluid balance in each patient. Before randomization (within 72 hours post-ictus) and after day-10 (from day 11th-14th, patient will only receive standard fluid therapy.

Intervention group (Albumin group)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age limits of participants will be between 18 and 80 years with either gender (male or female).
• Clinical presentation with the first of symptom of aSAH must be within 72 hours before randomization.
• Clinical manifestation must be suggestive of aSAH that may include classical thunderclap headache, cranial nerve deficits, changes in level of consciousness, neck rigidity and neurological deficits.
• All cases with WFNS grade 1 to 5 (at the time of randomization) will be recruited in the study.
• Head computed tomography demonstrates evidence of SAH (graded on Claassen's scale).
• Diagnostic cerebral angiography shows a saccular aneurysm/s, consistent with clinical presentation of SAH.
• Definitive treatment of ruptured aneurysm/s (with clipping or coiling of combined) must be carried out within 72 hours prior to randomization.
• An informed consent by patient or surrogate representative, must be duly signed and dated.

You may not qualify if:

• Timing of first symptom of SAH cannot be reliably ascertained.
• Cerebral angiogram negative SAH.
• Cerebral angiography showing mycotic/traumatic/fusiform aneurysm/s.
• Symptomatic vasospasm or angiographic (on TCD or CTA) sets in before recruitment within 72 hours.
• History of clinical findings/hospitalization due to heart failure within the past 6 months,
• Albumin administration prior to randomization in the same hospital admission.
• History of acute myocardial infarction (MI) within past 3 months.
• Any clinical presentations or electrocardiography (ECG) findings suggestive of acute MI on current admission.
• ECG evidence and/or clinical findings of 2nd or 3rd degree heart block or arrhythmias causing hemodynamic changes.
• Echocardiogram done before intervention/randomization showing an ejection fraction of \<40%.
• A creatinine level of \>2.0 mg/dl or a creatinine clearance of \<50 ml/min
• Pregnancy, lactation, or parturition within previous 30 days
• Any allergies to any ingredient in human albumin preparation.
• A prior severe physical disability (mRS \>2) that may hamper assessment of clinical outcome.
• Advanced chronic obstructive pulmonary diseases (with FEV1 \<50%) may manifest as frequent episodes significantly affecting the overall quality of life.

Sponsors & Collaborators

• Hamad Medical Corporation: lead

Study Sites (1)

Hamad General Hospital

Doha, Qatar

RECRUITING

Related Publications (3)

• Ali A, Rajeswaran AB, Shaikh N, Al-Rumaihi G, Al-Sulaiti G. Role of albumin-induced volume expansion therapy for cerebral vasospasm in aneurysmal subarachnoid hemorrhage: A systematic review. J Neurosci Rural Pract. 2023 Oct-Dec;14(4):582-590. doi: 10.25259/JNRP_372_2023. Epub 2023 Oct 3.

  PMID: 38059246 BACKGROUND

• Suarez JI, Shannon L, Zaidat OO, Suri MF, Singh G, Lynch G, Selman WR. Effect of human albumin administration on clinical outcome and hospital cost in patients with subarachnoid hemorrhage. J Neurosurg. 2004 Apr;100(4):585-90. doi: 10.3171/jns.2004.100.4.0585.

  PMID: 15070109 BACKGROUND

• Ali A, Khan M, Shaikh N, Mohamad AE, Al-Maadhadi M, Shah N, Al-Najjar Y, Salam A, Al-Rumaihi G, Ayyad A, Belkhair S, Al-Sulaiti G. Effectiveness of human albumin for clinical outcome in aneurysmal subarachnoid hemorrhages: a protocol for randomized controlled (HASH) trial. Trials. 2025 Feb 14;26(1):53. doi: 10.1186/s13063-025-08762-5.

  PMID: 39953562 DERIVED

MeSH Terms

Conditions

Subarachnoid Hemorrhage

Interventions

Serum Albumin, Human

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Serum Albumin; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Blood Proteins

Study Officials

• Arshad Ali, MBBS, MPH, FCPS, MSc

  Hamad Medical Corporation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Arshad Ali, MBBS, MPH, FCPS, MSc

CONTACT

(+974) 4439 2799; aali84@hamad.qa

Muhammad Mohsin Khan, MD, MSc

CONTACT

(+974) 4439 2440; mmkyousafzai@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant neurosurgery

Study Record Dates

• First Submitted: August 5, 2024
• First Posted: August 12, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: August 12, 2024

Record last verified: 2024-08

Locations

QA (1)