Study of beta blockers for salt wasting in patients with brain TB

ISRCTN ISRCTN16770388
DOI https://doi.org/10.1186/ISRCTN16770388
Submission date
11/09/2025
Registration date
26/09/2025
Last edited
12/09/2025
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
Tuberculous meningitis (TBM) is a serious brain infection caused by tuberculosis. TBM can cause serious problems in the brain, including increase volume of cerebrospinal fluid (CSF) leading to enlargement of brain’s hollow cavities (ventricles), strokes (especially in younger people), and convulsions. One common complication in TBM is hyponatremia, which means low levels of sodium in the blood. This happens in about one in three TBM patients. There are many reasons why sodium levels can drop, including poor appetite, vomiting, diarrhea, certain medications, and other health issues. In the past, a condition called SIADH (a condition where the body makes too much of a hormone called ADH) was thought to be the main reason for low sodium in TBM patients, but newer studies suggest that cerebral salt wasting (CSW) - a problem where the body loses too much salt due to brain stress - might actually be more common. CSW may be linked to the body's stress response, especially when there is brain pressure, infection, or stroke. One chemical involved in this stress response is called catecholamine. High levels of this chemical can cause the body to lose too much salt and water. Some research has shown that a type of medication called a beta blocker (which lowers stress signals in the body) may help improve outcomes in patients with brain injuries or stroke. Propranolol is one such beta blocker. In this study, we are testing whether propranolol can safely and effectively help to correct the low sodium levels and fluid loss in people with TBM-related CSW. We will compare it to standard care in a group of patients chosen at random.

Who can participate?
Patients aged between 15 to 70 years with TBM admitted during 2022 and 2024 in a tertiary care centre in India were screened for CSW

What does study involve?
The patients were randomly allocated to propranolol or placebo (saccharine). The intervention group received propranolol 10 mg twice daily on day one, which increased to 20 mg from day 2. Propranolol was continued until 1 month irrespective of correction of serum sodium; thereafter, gradually tapered within 2 weeks. Placebo group received a saccharine tablet in the similar manner.

What are possible benefits and risks of participating?
Propranolol is a drug used for reducing stress and to suppress catecholamine induced injury. Low serum sodium and high urinary output due to CSW may have early correction following adjunctive propranolol treatment. Hyponatremia is an independent risk factor of death in intensive care unit. Early correction of sodium and volume loss may reduce death and improve outcome. Propranolol is a drug used in medical practice for long time. It has a side effect profile including slowing of heart rate and reduction in blood pressure. The pulse and blood pressure will be monitored closely and in case of such side effects, the drug will be withdrawn.

Where is the study run from?
Sanjay Gandhi Post Graduate Institute of Medical Sciences (India)

When is the study starting and how long is it expected to run for?
March 2022 to December 2024

Who is funding the study?
Investigator initiated and funded

Who is the main contact?
Jayantee Kalita, jkalita@sgpgi.ac.in, jayanteek@yahoo.com

Contact information

Prof Jayantee Kalita
Public, Scientific, Principal Investigator

Department of Neurology, C-block
Sanjay Gandhi Post Graduate Institute of Medical Sciences
Raebareli Road
Lucknow
226014
India

ORCiD logoORCID ID 0000-0002-6141-3592
Phone +91 (0)5222494177
Email jkalita@sgpgi.ac.in

Study information

Study designInvestigator-initiated single center open-label randomized placebo-controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment, Safety, Efficacy
Participant information sheet 47982_PIS.pdf
Scientific titleRole of beta blockers in cerebral salt wasting in the patients with tuberculous meningitis: an open labelled randomized control trial
Study acronymBEST - TBM
Study objectivesPrimary objective:
Number of days to normalize serum sodium

Secondary objective:
1. Number of days to achieve positive fluid balance
2. Number of days to have 3 l urinary output
3. Mortality at 1 month
4. Side effects
5. Functional outcome was assessed at 3 and 6 months using a modified Rankin Scale (mRS), and categorized as good (mRS score <3) and poor (mRS score 3 to 6)
Ethics approval(s)

Approved 11/03/2022, Institutional Ethics Committee, Sanjay Gandhi Post Graduate Institute of Medical Sciences (Raebareli Road, Lucknow, 226014, India; +91 (0)522-2494918, +91 (0)522 2668017; iec@sgpgi.ac.in), ref: 2021-225-DM-122

Health condition(s) or problem(s) studiedCerebral salt wasting syndrome in patients with tuberculous meningitis
InterventionOnce the diagnosis of cerebral salt wasting syndrome was ascertained in the patients with tuberculous meningitis, the patients were randomized to propranolol or placebo (saccharine) using simple randomization with a 1:1 allocation ratio. The intervention group received propranolol 10 mg twice daily on day one, which increased to 20 mg from day two. Propranolol was continued until 1 month irrespective of correction of serum sodium; thereafter, gradually tapered within 2 weeks. The placebo group received saccharine tablet in the similar manner.
Intervention typeDrug
Pharmaceutical study type(s)Dose response
PhasePhase II
Drug / device / biological / vaccine name(s)Propranolol
Primary outcome measureThe number of days for normalization of serum sodium: serum sodium levels were measured every third day for up to 1-month post-randomization, at 1 month, 3 months and 6 months follow-up
Secondary outcome measures1. Number of days to achieve 500 ml positive fluid balance (Intake- output >500 ml). Daily fluid balance (intake and output over 24 hours) was recorded to monitor fluid status.
2. Number of days to have <3 L urinary output. Daily fluid balance (intake and output over 24 hours) was recorded to monitor fluid status.
3. Mortality recorded at 1 month
4. Side effects recorded during hospitalization and at follow-up visits at 1 month, 3 months, and 6 months
5. Functional outcome assessed using a modified Rankin Scale (mRS) and categorized as good (mRS score < 3) and poor (mRS score 3 to 6) at 3 and 6 months
Overall study start date11/03/2022
Completion date15/12/2024

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit15 Years
Upper age limit70 Years
SexBoth
Target number of participants38
Total final enrolment38
Key inclusion criteriaPatients aged between 15 to 70 years with tuberculous meningitis and having cerebral salt wasting syndrome (CSW)

Diagnostic criteria of tuberculous meningitis

Essential criteria:
The clinical features of meningitis (fever, headache, vomiting) for more than 2 weeks

Supportive criteria:
1. Cranial imaging: CT/MRI evidence of excaudate, hydrocephalous, granulomas in isolation or in combination
2. Cerebrospinal fluid: cells 10-500/mmb, lymphocytic predominance, protein >1 g/liter
3. Evidence of extra CNS active tuberculosis
4. Exclusion of alternative diagnosis of meningitis

The diagnosis of CSW was based on the following essential and supportive criteria

Essential criteria, all are mandatory
1. Polyuria (>3 l/day for two consecutive days)
2. Serum sodium <135 mEq/L in two consecutive tests 24 hours apart
3. Absence of secondary causes of hyponatremia such as renal, hepatic or cardiac failure, endocrinal disorder, natriuretic drugs etc

Supportive criteria: three out of five are needed
1. Clinical incidence of hypovolemia: dry skin, hypotension, tachycardia or postural hypotension
2. Consistent fluid deficit on intake output chart
3. Laboratory evidence of dehydration such as elevated hematocrit, hemoglobin, albumin and blood urea
4. Central venous pressure less than 6 cm of water
5. Urinary sodium more than 40 mEq/L or urine osmolality more than 300 mOsmol/L on two consecutive days
Key exclusion criteria1. Patients with endocrinal disorder, organ (renal, liver, heart) failure, vasculities, renal tubular acidosis, malignancy, pregnancy, lactation, on chemotherapy, radiotherapy, inotrope, dopaminergic, antidopaminergic, diuretics, carbamazepine, mannitol or aminoglycosides
2. Above 70 years and below 15 years of age
3. Denial of consent
4. Patients requiring mechanical ventilation or cardiopulmonary resuscitation
Date of first enrolment12/03/2022
Date of final enrolment15/12/2024

Locations

Countries of recruitment

  • India

Study participating centre

Sanjay Gandhi Post Graduate Institute of Medical Sciences
Raebareli Road
Lucknow
226014
India

Sponsor information

Funders

Funder type

Other

Investigator initiated and funded

No information available

Results and Publications

Intention to publish date12/12/2025
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planPlanned publication in a peer- reviewed journal
IPD sharing planThe datasets generated during and analysed during the current study will be available upon request from Jayantee Kalita (jkalita@sgpgi.ac.in, jayanteek@yahoo.com)

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Participant information sheet 12/09/2025 No Yes
Statistical Analysis Plan 12/09/2025 No No

Additional files

47982_PIS.pdf
47982_SAP.pdf

Editorial Notes

12/09/2025: Study's existence confirmed by the Institutional Ethics Committee, Sanjay Gandhi Post Graduate Institute of Medical Sciences.