2/17/23, 5:19 PM Acute Ischemic Stroke Thrombolysis with Tenecteplase: An Institutional Experience from South India - PMC

Ann Afr Med. 2018 Apr-Jun; 17(2): 90–93. PMCID: PMC5875126

doi: 10.4103/aam.aam_50_17: 10.4103/aam.aam_50_17 PMID: 29536964

Language: English | French

Acute Ischemic Stroke Thrombolysis with Tenecteplase: An Institutional Experience

from South India
Mohammed Owais, Ajay Panwar,1 Chandrasekhar Valupadas, and Madhavarao Veeramalla1

Department of Medicine, Kakatiya Medical College and Mahatma Gandhi Memorial Hospital, Warangal, Telangana,
India
1
Department of Neurology, Kakatiya Medical College and Mahatma Gandhi Memorial Hospital, Warangal,
Telangana, India
Address for correspondence: Dr. Ajay Panwar, Department of Neurology, Kakatiya Medical College and Mahatma
Gandhi Memorial Hospital, Warangal, Telangana, India. E-mail: [email protected]

Copyright : © 2018 Annals of African Medicine

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Abstract

Objective:

Outcome assessment of intravenous (IV) thrombolysis with tenecteplase in acute ischemic

stroke.

Materials and Methods:

We consecutively enrolled acute ischemic stroke patients who underwent IV thrombolysis with
tenecteplase from October 2016 to May 2017. Primary clinical efficacy outcome was defined as
an improvement in the National Institute of Health Stroke Scale (NIHSS) score of ≥4 points at
24 h (h). Secondary clinical efficacy outcome was the favorable outcome on modified Rankin
scale at 90 days defined as a score of 0 or 1. The safety endpoints were death rate at 90 days
and symptomatic intracranial hemorrhage (SICH).

Results:

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2/17/23, 5:19 PM Acute Ischemic Stroke Thrombolysis with Tenecteplase: An Institutional Experience from South India - PMC

Mean NIHSS scores at baseline and 24 h were 13 (±3.81) and 9.29 (±5.74), respectively, the dif‐
ference being statistically significant (P = 0.016). In this study, nine patients (64%) met the pri‐
mary clinical efficacy outcome and eleven (78.5%) patients met the secondary clinical efficacy
outcome. Only 1 (7%) patient developed SICH and additionally, aspiration pneumonia with sub‐
sequent death.

Conclusion:

This study confirms the efficacy and safety of tenecteplase for stroke thrombolysis in our clini‐
cal setting. Tenecteplase appears to be a suitable option for stroke thrombolysis in resource-
limited settings, considering its cost-effectiveness, and ease of administration.

Keywords: Acute ischemic stroke, alteplase, tenecteplase, thrombolysis, AVC isché mique aigu,
alteplase, tenecteplase, thrombolyse

Introduction

Intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA) has as‐
sumed vital importance in the successful treatment of acute ischemic stroke. Conventionally, al‐
teplase infusion has proved to be efficacious in improving the functional outcomes when given
within 4.5 h (h) of the stroke onset, and it is the only worldwide approved rt-PA agent for
stroke thrombolysis.[1,2] However, recent randomized controlled trials (RCTs) have compared
the results of alteplase and tenecteplase in stroke thrombolysis and observed tenecteplase to
have an efficacy and safety at least, similar or superior to alteplase.[3,4,5] Besides,
tenecteplase has some pharmacological advantages in comparison to alteplase. It has a longer
duration of action and higher fibrin specificity. Further, it can be given as a single bolus injec‐
tion, unlike alteplase which is given as a continuous infusion after the bolus dose, thus offering
the advantage of a convenient administration. Based on these advantages and the results of
above-mentioned RCTs, tenecteplase has been recently approved for ischemic stroke throm‐
bolysis in India within 3 h of the stroke onset. Moreover, it offers the additional benefit of rea‐
sonable pricing, being available at a cost which is nearly half of the alteplase. A low-cost rt-PA
agent with an ease of administration offers a great potential to tackle the stroke epidemic in
developing countries like India. Thus, in consequence to its recent approval for stroke throm‐
bolysis and owing to its free availability under hospital's medicines indenting scheme, we
planned to start stroke thrombolysis with tenecteplase (Metalyse®) at our tertiary hospital. We
report our observations from Kakatiya Medical College and associated Mahatma Gandhi
Memorial Hospital (MGMH) at Warangal, which is a government-run tertiary care referral
health center in Telangana region of South India. MGMH is served by well-established intensive
and acute medical care units, along with a regular neurology outpatient department. The ma‐
jority of patients attending our hospital belong to the rural population, who often cannot af‐
ford the high cost of alteplase. Hence, with the approval of tenecteplase for stroke thromboly‐
sis, we hoped to realize the goal of improved stroke management for our impoverished
patients.

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Materials and Methods

The present study was a prospective observational study which was conducted from October
2016 to May 2017. During the study, we enrolled all the ischemic stroke patients who under‐
went thrombolysis with tenecteplase.

Inclusion and exclusion criteria

We enrolled patients more than 18 years of age who were diagnosed with acute ischemic
stroke, had the National Institute of Health Stroke Scale (NIHSS) score >4, and a modified
Rankin scale (mRS) score of ≤2 before the stroke onset.[4] We used baseline computed tomog‐
raphy (CT) scan of the brain in all cases to rule out intracranial hemorrhage. Further, other
classical contraindications for alteplase thrombolysis were used as exclusion criteria.[1]

Respecting the time window of its approval for stroke thrombolysis, we used tenecteplase
within 3 h of the stroke onset. Informed consent was obtained in all cases after discussing ben‐
efits and the risk of a hemorrhagic event associated with thrombolytic therapy. Tenecteplase
was administered as a single bolus IV injection at the dose of 0.2 mg/kg, with total dose not ex‐
ceeding 20 mg.

Outcomes

We defined the primary clinical efficacy outcome as improvement in NIHSS score of 4 or more
points after 24 h.[6] Secondary clinical efficacy outcome was disability assessment at 90 days
based on mRS score, dichotomized as a favorable outcome (with a score of 0 or 1) or an unfa‐
vorable outcome (a score of 2–6).[2] The safety endpoints were death rate at 90 days and
symptomatic intracranial hemorrhage (SICH), which is defined as any fresh intracranial bleed‐
ing resulting in clinical worsening with a decline of >4 points in score on NIHSS or death, as
per European Cooperative Acute Stroke Study III study protocol.[2]

Clinical assessment

All the acute ischemic stroke patients were assessed by an internal medicine resident in medi‐
cal emergency on a priority basis. Those presenting in the window period for thrombolysis un‐
derwent a quick evaluation to rule out the contraindications to thrombolysis through medical
history, blood pressure, premorbid mRS score and NIHSS score assessment. Simultaneously,
capillary blood glucose estimation was done and blood samples were withdrawn for other
standard laboratory tests as mentioned in the exclusion criteria for thrombolysis. Soon after,
patients were shifted for an urgent CT scan of the brain. The patients having no evidence of in‐
tracranial hemorrhage were thrombolyzed according to above-mentioned protocol. All the pa‐
tients receiving rt-PA were closely monitored for heart rate, blood pressure, and oxygen satu‐
ration for initial 24 h. NIHSS scores were calculated at baseline, 2 h, and 24 h post-thromboly‐
sis while mRS scores assessment was done at baseline and 90-day post-thrombolysis.

Follow-up brain imaging

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Any patient who showed neurological deterioration with an NIHSS score decline of ≥4 points
was made to undergo an urgent CT scan to rule out SICH. In addition, all the patients receiving
tPA underwent CT or magnetic resonance imaging of the brain within 24–48 h post-
thrombolysis.

Variables and data entry

Variables including the time of stroke onset, onset-to-door time, door-to-imaging, and door-to-
needle time were entered into well-structured case forms. Other data including demographic
details, risk factors for stroke, vital signs, details of neurological examination including NIHSS
and mRS scores, and laboratory parameters were also recorded. Data were entered into
“Microsoft Excel” and “SPSS version 16.0” (SPSS Inc., Chicago, IL, USA) was used for statistical
analysis.

Results

During the study, a total of 14 patients underwent IV stroke thrombolysis with tenecteplase.
Mean age was 60.7 years with 71% of the study subjects being males. Hypertension was the
commonest risk factor present in 57% of the cases, followed by dyslipidemia in 50%. Most of
the patients had large artery stroke subtype, with the infarct region belonging to the territory
of middle cerebral artery in all the 14 cases. The mean time from onset of symptoms to arrival
at the medical emergency was 116 (±24.11) minutes (min) while mean “door to needle” time
was 57 (±18.47) min. The study subjects had a mean NIHSS score of 13 (±3.81) and a median
mRS score of 5 (range: 3–5) at the baseline [Table 1].

Outcome analysis

In our study, nine patients (64%) met the primary clinical efficacy outcome with an improve‐
ment in NIHSS score of 4 or more points at 24 h. Mean NIHSS scores at 2 h and 24 h were
10.57 (±5.14) and 9.29 (±5.74), respectively. We used “one-way repeated measures analysis of
variance” test and observed a significant difference between the NIHSS scores at baseline and
24 h (P = 0.016) [Table 2]. Further, 11 (78.5%) patients in our study achieved a favorable out‐
come on disability assessment at 90 days with an mRS score of 0 or 1, thus meeting the sec‐
ondary clinical efficacy outcome of the study. Only 1 (7%) patient developed an adverse event
in the form of SICH. The same patient also developed aspiration pneumonia and subsequently
died.

Discussion

At present, the “incidence” and “case fatality rate” of stroke is higher in low- and middle-in‐
come countries according to the results of recently published Prospective Urban Rural
Epidemiology study.[7] The stroke epidemic has recently arrived in India and is now a major
health burden for our nation.[8] There are several barriers to acute stroke management in
India including recognition of stroke symptoms, prehospital delays, inadequate ambulance ser‐
vices, and cost of tPA. Among these, the high cost of conventionally used tPA (alteplase) is the
major hurdle for depriving the impoverished of getting a successful stroke treatment. The
present study reconfirmed the efficacy and safety profile of tenecteplase in acute ischemic
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stroke, as observed in other recent studies. In our study, 64% (9/14) patients met the primary
clinical efficacy outcome by achieving an improvement in NIHSS score of 4 or more points at
24 h and 78.5% (11/14) met the secondary clinical efficacy outcome by having an mRS score
of 0 or 1 at 90 days. In another single arm study respecting tenecteplase in stroke, Belkouch et
al. reported a 24 h improvement of NIHSS score by >4 points in 77% (10/13) cases.[6] Among
Indian patients, none of the studies have reported the results of tenecteplase in stroke throm‐
bolysis so far. However, our observations regarding the efficacy of Tenecteplase are similar to
the results of previous Indian data regarding alteplase. Durai Pandian et al. from All India
Institute of Medical Sciences reported 65% patients to have an improvement of 4 or more
points in NIHSS score at 48 h with alteplase.[9] We observed highly significant difference be‐
tween NIHSS scores at baseline and 24 h (P = 0.006) which is in agreement with the previously
published studies on tenecteplase.[4] In the present study, 78.5% patients had an excellent re‐
covery at 90 days with mRS score being 0 or 1, which is even better than the results of a recent
RCT in which excellent recovery was observed in 54% subjects.[4] One patient (7%) in our
study developed SICH and additionally, aspiration pneumonia with subsequent death. This rate
of adverse event with tenecteplase thrombolysis is in line with the previous studies.

Thus, the results of our study reiterate the previous observations that tenecteplase is an effec‐
tive and safe rt-PA agent for acute ischemic stroke thrombolysis.[4,10] However, the study has
several limitations. First, we observed the results in a small number of patients and the find‐
ings need to be confirmed with a larger sample size. Second, ours was a single arm study with
tenecteplase; however, a randomized comparison with alteplase is required to obtain a realistic
data for our patients. Further, we performed IV thrombolysis with tenecteplase within 3 h of
the symptoms onset, however, the benefits need to be confirmed in the extended time window
of 4.5 h, as observed in other studies. Respecting these limitations, a matched comparative
study of alteplase versus tenecteplase in acute ischemic stroke is underway at our hospital.

Conclusion

Tenecteplase appears to be a safe and efficacious agent for stroke thrombolysis. Considering
its significantly low price and ease of administration, tenecteplase seems to be a suitable
thrombolytic agent for stroke patients in developing countries.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for
acute ischemic stroke. N Engl J Med. 1995;333:1581–7. [PubMed: 7477192]

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2. Hacke W, Kaste M, Bluhmki E, Brozman M, Dávalos A, Guidetti D, et al. Thrombolysis with alteplase 3 to 4.5 hours
after acute ischemic stroke. N Engl J Med. 2008;359:1317–29. [PubMed: 18815396]

3. NOR-TEST: Tenecteplase Similar to Alteplase in Stroke – Medscape; 19 May. 2017. [Last accessed on 2017 Jun 27].
Available form: https://www.medscape.com/viewarticle/880251 .

4. Parsons M, Spratt N, Bivard A, Campbell B, Chung K, Miteff F, et al. A Randomized trial of tenecteplase versus
alteplase for acute ischemic stroke. N Engl J Med. 2012;366:1099–107. [PubMed: 22435369]

5. Huang X, Cheripelli BK, Lloyd SM, Kalladka D, Moreton FC, Siddiqui A, et al. Alteplase versus tenecteplase for
thrombolysis after ischaemic stroke (ATTEST): A phase 2, randomised, open-label, blinded endpoint study. Lancet
Neurol. 2015;14:368–76. [PubMed: 25726502]

6. Belkouch A, Jidane S, Chouaib N, Elbouti A, Nebhani T, Sirbou R, et al. Thrombolysis for acute ischemic stroke by
tenecteplase in the emergency department of a Moroccan hospital. Pan Afr Med J. 2015;21:37. [PMCID: PMC4564430]
[PubMed: 26405473]

7. Yusuf S, Rangarajan S, Teo K, Islam S, Li W, Liu L, et al. Cardiovascular risk and events in 17 low-, middle-, and high-
income countries. N Engl J Med. 2014;371:818–27. [PubMed: 25162888]

8. Pandian JD, Sudhan P. Stroke epidemiology and stroke care services in India. J Stroke. 2013;15:128–34. [PMCID:
PMC3859004] [PubMed: 24396806]

9. Durai Pandian J, Padma V, Vijaya P, Sylaja PN, Murthy JM. Stroke and thrombolysis in developing countries. Int J
Stroke. 2007;2:17–26. [PubMed: 18705983]

10. Haley EC, Jr, Lyden PD, Johnston KC, Hemmen TM TNK in Stroke Investigators. A pilot dose-escalation safety study
of tenecteplase in acute ischemic stroke. Stroke. 2005;36:607–12. [PubMed: 15692126]

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Figures and Tables

Table 1

Baseline characteristics of 14 patients thrombolyzed with tenecteplase

Variables Values (%)

Age (years, mean±SD) 60.71±9.21

Gender (male) 10 (71.4)

Risk factors

Hypertension 8 (57)

Dyslipidemia 7 (50)

Diabetes mellitus 3 (21)

Smoking 3 (21)

Stroke subtype

Large artery 10 (71)

Lacunar 4 (29)

Cerebral circulation

Anterior cerebral artery 0

Middle cerebral artery 100 (100)

Posterior cerebral artery 0

Laterality

Left hemisphere 8 (57)

Right hemisphere 6 (43)

Onset to door time (min, mean±SD) 116±24.11

Door to imaging time (min, mean±SD) 38±18.98

Door to needle time (min, mean±SD) 57±18.47

Baseline NIHSS score (mean±SD) 13±3.81

Baseline mRS score (median) 5

NIHSS=National Institute of Health Stroke Scale, mRS=Modified Rankin Scale, SD=Standard deviation

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Table 2

Outcome analysis after tenecteplase thrombolysis

Variables Values Significance of difference from baseline (P)

NIHSS score (mean±SD)

Baseline 12.93±3.81

2h 10.57±5.14 0.061*

24 h 9.29±5.74 0.016*

mRS score (median)

Baseline 5

90 days 1 0.001†

*One-way repeated measures ANOVA, †Wilcoxon signed-rank test. NIHSS=National Institute of Health Stroke Scale,
mRS=Modified Rankin scale, SD=Standard deviation

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