Net scan Clinical trials on Indomethacin

Indomethacin in Alzheimers disease

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16697488&itool=iconabstr &query_hl=2&itool=pubmed_docsum

NSAIDs and Alzheimer disease: Epidemiological, animal model and clinical studies. McGeer PL, McGeer EG. Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada.

This review reports correlations between four independent fields related to inflammation and Alzheimer disease: fundamental pathology, epidemiology, transgenic animal studies and clinical trials. Activated microglia, along with a spectrum of inflammatory mediators, have been identified in association with the lesions of Alzheimer disease (AD), suggesting that antiinflammatory agents such as NSAIDs should protect against the disease. In multiple epidemiological investigations testing this hypothesis, a significant risk reduction, or a trend towards such a reduction has been observed in long term as opposed to short term users of traditional NSAIDs. In studies where such NSAIDs have been administered to AD transgenic mice, a dose dependent reduction in pathology was observed. The selective C0X-2 inhibitors were ineffective. Results of clinical investigations have so far been disappointing but have nevertheless correlated with fundamental pathological findings and with transgenic mouse results. Four clinical trials using selective COX-2 inhibitors failed which is in keeping with the animal results and is consistent with pathological findings demonstrating that COX-1 and not COX-2 is the appropriate target in activated human microglia. A low dose trial of the traditional NSAID naproxen also failed, but pilot trials using therapeutically established doses of indomethacin and Diclofenac / misoprostol showed promise. Further clinical investigations with relatively high doses of traditional NSAIDs might be warranted, although significant side effects should be anticipated.

Indomethacin in Alzheimer's disease

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=11060701&itool=iconabstr &query_hl=2&itool=pubmed_DocSum

Anti-inflammatory drugs: a hope for Alzheimer's disease?

Hull M, Lieb K, Fiebich BL.

Department of Psychiatry, University of Freiburg Medical School, Hauptstr. 5, D - 79104 Freiburg, Germany. Human brain cells are capable of initiating and amplifying a brain specific inflammatory response involving the synthesis of cytokines, acute-phase proteins, complement proteins, prostaglandins and oxygen radicals. In Alzheimer's disease (AD), all signs of an inflammatory microglial and astroglial activation are present inside and outside amyloid depositions and along axons of neurones with neurofibrillary tangles. Cell culture and animal models suggest a bidirectional relationship between inflammatory activation of glial cells and the deposition of amyloid. Although it remains unclear which of the different pathophysiological processes in AD may be the driving force in an individual case, the inflammatory activation may increase the speed of cognitive decline. Epidemiological studies point to a reduced risk of AD among users of anti-inflammatory drugs. Therefore, anti-inflammatory drugs have become the focus of several new treatment strategies. A clinical trial with the non-steroidal anti-inflammatory drug (NSAID) indomethacin showed promising results, while a clinical trial with steroids did not show a beneficial effect. Further trials with NSAIDs such as unselective cyclooxygenase (COX) and selective cyclooxygenase-2 (COX-2) inhibitors are on their way. COX inhibitors may not only act on microglial and astroglial cells but also reduce neuronal prostaglandin production. New data suggest that prostaglandins enhance neurotoxicity or induce pro-inflammatory cytokine synthesis in astroglial cells. Amongst these promising new strategies to reduce microglial or monocyte activation, interfering with intracellular pathways has been shown to be effective in various cell culture and animal models but clinical studies have not yet been performed.

Indomethacin in brain injury

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16573440&itool=iconabstr &query_hl=2&itool=pubmed_docsum

Indomethacin--a review of its role in the management of traumatic brain injury Roberts RG, Redman JW.

Critical Care Directorate, richroberts@doctors.org.uk

University

Hospital

of

Wales,

Cardiff,

United

Kingdom.

OBJECTIVE: To review the use of indomethacin in the management of traumatic brain injury. DATA SOURCES: Articles reported from 1966 to 2001 and identified through a MEDLINE search of the English language literature on the use of indomethacin in traumatic brain injury. SUMMARY OF REVIEW: Traumatic brain injury (TBI) is a frequent cause of mortality and morbidity in patients with head injury. The use of indomethacin in treating raised intracranial pressure (ICP) secondary to TBI is controversial. Clinical studies suggest that it may be useful in the management of intracranial hypertension, when used in combination with standard techniques, by decreasing cerebral blood flow and reducing ICP during the restoration of the blood brain barrier. Its unique mechanism of action may be due to precapillary vasoconstriction, which reduces the transcapillary transfer of fluid into the cerebral extracellular space. However, large, prospective, randomised and controlled studies have not yet been performed to confirm its benefit in patients with TBI. CONCLUSIONS: Indomethacin should only be considered as an experimental therapy for refractory intracranial hypertension in TBI patients, as current evidence is not available to support its routine use in the management of an elevated ICP. Its use in patients with cerebral vasospasm, renal failure, bleeding disorders, peptic ulceration and coagulopathies is contraindicated.

Indomethacin in brain injury

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=9337126&itool=iconabstr& query_hl=2&itool=pubmed_DocSum

Indomethacin in the management of elevated intracranial pressure: a review. Harrigan MR, Tuteja S, Neudeck BL. Department of Surgery, University of Michigan Medical Center, and College of Pharmacy, Ann Arbor, USA. Elevated intracranial pressure occurs frequently in patients with severe head injury. A number of studies in recent years suggest that indomethacin may be useful in the management of elevated intracranial pressure. Indomethacin acts primarily by reducing cerebral blood flow and decreasing cerebral edema following head injury. This review summarizes the basic and clinical studies of the effects of indomethacin on cerebral blood flow, brain edema, and intracranial pressure. The pharmacology of indomethacin, and issues for future investigation in the use of indomethacin in severe head injury, are discussed.

Indomethacin in cancer

http://www.cancerhelp.org.uk/help/default.asp?page=10421

Non steroidal anti inflammatory drugs Some scientists believe that malnutrition and cancer cachexia may be a response to inflammation caused by the presence of a tumour in the body. This has led to research into using non steroidal anti inflammatories (NSAIDs) to helping prevent and treat malnutrition in people with cancer. One small trial of 135 patients with cancer who had severe malnutrition showed that an NSAID called indomethacin may help. Half the patients were given indomethacin and half a dummy pill (placebo). Those who took indomethacin had better overall survival. More trials are needed in this area before we will know how well this type of treatment will work.

Indomethacin in cancer
http://www2.ccc.uab.edu/CSUWEB/ClinicalTrialsListing.asp

Role of indomethacin in cancers of the Head and Neck, Hypopharynx, Larynx, Oral cavity & Oropharynx

Protocol Number:

UAB 0529

Title A Phase 2, Open-Label Trial of the Safety and Biological Effect of Pre-Operative Perilymphatic Ultra Low Dose IRX-2 (with Cyclophosphamide, Indomethacin and Zinc) in Patients with Locally Advanced, Resectable Cancer of the Head and Neck Principal Investigator Carroll Phone (205) 975-9289

Indomethacin in cancer

http://www.mdanderson.org/Departments/Neuro/dIndex.cfm?pn=77B0F7337F67-11D4-AEC800508BDCCE3A

Neurocognitive Outcomes and Central Nervous System Inflammation in High Grade Glioma Patients Treated with Indomethacin While Undergoing Radiation - A Pilot Study
The goal of this clinical research study is to learn if indomethacin can help to decrease inflammation of the brain, short term memory loss, and the ability to think and reason clearly, in patients with high-grade brain tumors or metastatic lung or melanoma brain tumors, who are receiving brain radiation. The safety of this treatment will also be studied. Study objectives To estimate the magnitude of cognitive impairment in high-grade glioma patients (newly diagnosed anaplastic astrocytoma and glioblastoma multiforme) or metastatic brain tumors (lung or melanoma) undergoing brain conformal radiation (CR) treated with indomethacin versus placebo and to determine the variability of inflammatory cytokines within the cerebral spinal fluid (CSF), this pilot data will be used to develop a multiinstitutional trial to determine if there is a statistical difference in the neurocognitive performance scores between patients who receive indomethacin versus placebo at 0, 3, 6 months, 1, 1.5 and 2 years after brain CR and to correlate this with a decrease in central nervous system (CNS) inflammation (i.e. microglia activation and proliferation) by examining CSF levels of IL-1, IL-6, and TNF.

Indomethacin in postoperative pain

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=8280405&itool=iconabstr& query_hl=2&itool=pubmed_DocSum

A risk-benefit appraisal of injectable NSAIDs in the management of postoperative pain

Nuutinen LS, Laitinen JO, Salomaki TE Department of Anaesthesiology, University Hospital of Kuopio, Finland. The inadequacy of pain treatment has been demonstrated in many patient groups suffering from acute pain. The injectable nonsteroidal anti-inflammatory drugs (NSAIDs), including indomethacin, diclofenac, ketoprofen and ketorolac, provide relief from the pain associated with several different conditions. When administered alone or in combination with low doses of opioids, NSAIDs provide good pain relief after musculoskeletal trauma or operation. The main advantage of these agents is that they may form the first-line therapy for pain relief and thus decrease the need of opioids. This avoids respiratory depression which can be associated with opioids. In contrast to opioids, NSAIDs do not cause respiratory depression or have marked adverse effects on the central nervous system. However, they may be associated with adverse effects of the gastrointestinal tract, liver and kidneys, and may increase pre- and postoperative bleeding and cause allergic reactions. These effects are related to the ability of NSAIDs to inhibit prostaglandin synthesis. Use of NSAIDs has to be considered carefully in patients with asthma, allergy to aspirin and NSAIDs, atopy, peptic ulcer or bleeding disorders (such as abnormalities in blood coagulation or coagulation deficits). These considerations are especially important in elderly patients. Having taken these contraindications into account, many clinical studies have demonstrated that NSAIDs are at least as safe as opioids when administered in the short term. However, few studies have specifically monitored adverse effects or included patients over 65 to 70 years of age. In addition, patients with risk factors have often been excluded from the trials. Therefore, the risk-benefit ratio of NSAIDs requires further assessment.

Indomethacin in psoriasis

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Drugs in exacerbation of psoriasis

Abel EA, DiCicco LM, Orenberg EK, Fraki JE, Farber EM

Drugs that have been associated with the precipitation or exacerbation of psoriasis include lithium, beta adrenergic receptor blocking agents, and antimalarials. The withdrawal of corticosteroids has been reported to activate pustular psoriasis. Nonsteroidal anti-inflammatory drugs, such as indomethacin, have recently been reported to exacerbate psoriasis, although additional wellcontrolled studies are still needed. Drugs used for treatment of psoriasis will sometimes cause a flare because of irritation, phototoxicity, or hypersensitivity reaction resulting in a Koebner phenomenon. Because psoriasis is a very complex disease and its activity is often unpredictable, clinical studies on adverse drug effects on psoriasis have been difficult to conduct. This review evaluates clinical, histologic, and biochemical evidence in the literature for drug-associated onset or exacerbation of psoriasis.

Chrono pharmacokinetics of Indomethacin

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Chronopharmacokinetic study of a prolonged release form of indomethacin
Guissou P, Cuisinaud G, Llorca G, Lejeune E, Sassard J. The chronopharmacokinetics of indomethacin was studied in patients with rheumatoid diseases after a single oral dose of a new prolonged-release form containing indomethacin 75 mg. The drug was given either at 8, 12 or 20 h and its plasma concentrations, as well as those of its main metabolite, O-desmethyl indomethacin, were followed using a new specific gas chromatographic assay. When given at 20 h plasma indomethacin concentrations did not exhibit a sharp peak and remained much more stable than when the drug was given at 8 or 12 h. In addition, plasma Odesmethyl indomethacin was significantly higher after administration of indomethacin at 20 h than at 8 or 12 h. It is concluded that the pharmacokinetics of the oral prolonged-release form of indomethacin exhibited chronobiological variation. The data are in accordance with clinical studies which suggest that it might be worthwhile to administer this formulation of indomethacin at 20 h.

Indomethacin topical after eye surgery

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=959 9360

A prospective randomized trial of topical soluble 0.1% indomethacin versus 0.1% diclofenac versus placebo for the control of pain following excimer laser photorefractive keratectomy
Guissou P, Cuisinaud G, Llorca G, Lejeune E, Sassard J. The chronopharmacokinetics of indomethacin was studied in patients with rheumatoid diseases after a single oral dose of a new prolonged-release form containing indomethacin 75 mg. The drug was given either at 8, 12 or 20 h and its plasma concentrations, as well as those of its main metabolite, O-desmethyl indomethacin, were followed using a new specific gas chromatographic assay. When given at 20 h plasma indomethacin concentrations did not exhibit a sharp peak and remained much more stable than when the drug was given at 8 or 12 h. In addition, plasma ODepartment of Ophthalmology, Hotel-Dieu de Paris, INSERM U86, University of Paris VI, Medical School, France. BACKGROUND AND OBJECTIVE: To compare the safety and efficacy of topical nonsteroidal antiinflammatory drugs (NSAIDs) for the control of pain after excimer laser photorefractive keratectomy (PRK). PATIENTS AND METHODS: One hundred twenty informed patients were enrolled in a double-masked, randomized, comparative study and assigned to either 0.1% indomethacin, 0.1% diclofenac, or placebo treatment. Subjective postoperative pain, symptoms, reepithelialization rate, and systemic medications were monitored for 2 days following photoablation. RESULTS: Compared with the placebo, 0.1% indomethacin solution significantly reduced pain on the day of surgery (D0) (P < .05), whereas 0.1% diclofenac did not reach a significant level (P = . 46). At D0, analgesic intake by the oral route was significantly greater in the placebo group (P < . 05). Severe photophobia was significantly less frequent in the group treated with 0.1% indomethacin (P < .05). Corneal wound healing was significantly delayed in the patients treated with 0.1% diclofenac at D2 as compared with other groups (P = .04). CONCLUSION: Topical 0.1% indomethacin solution helps control the pain induced by excimer laser photoablation of the cornea without any detrimental effect to the corneal epithelial wound healing

Indomethacin topical vs dexamethasone solution

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=100 30555

Am J Ophthalmol. 1999 Feb;127(2):148-52

Topical indomethacin solution versus dexamethasone solution for treatment of inflamed pterygium and pinguecula: a prospective randomized clinical study
Department of Ophthalmology, Hadassah University Hospital, Jerusalem, Israel.

PURPOSE: To compare the effect of topical indomethacin 0.1% solution with the effect of topical dexamethasone 0.1% phosphate solution on signs and symptoms of inflamed pterygium and pinguecula. METHODS: Of 50 consecutive patients who had inflamed pterygia (n = 17) or pingueculae (n = 33), met the study criteria, and signed an informed consent, one eye of each patient was evaluated in a comparative, prospective, randomized, double-masked, controlled study. Objective signs (conjunctival congestion, redness and edema, and staining of cornea) and subjective complaints (photophobia, pain, foreign-body sensation, discomfort, and tearing) were evaluated and scored. We also evaluated "total signs," "total symptoms," and "total score." Group 1 (n = 25) received topical indomethacin 0.1% solution, and group 2 (n = 25) received a topical dexamethasone phosphate 0.1% solution six times daily for 3 days, then four times daily over the following 11 days. Patients were examined before treatment, on days 3, 7, and 14 after the treatment was initiated, and 2 and 4 weeks after the treatment was discontinued. RESULTS: In both groups, the scores for "total signs," "total symptoms," and "total score" were significantly lower (P = .001) by day 14. There were no differences between groups 1 and 2 for "total signs," "total symptoms," and "total score" at days 3, 7, and 14 (P = .07 to P = .88). After treatment was discontinued, the dexamethasone-treated group experienced a significantly greater recurrence of "total signs" (P = .023 at day 30, P = .02 at day 45), but there was no statistically significant difference in "total symptoms" and "total score." Patients in group 2 reported more stinging after drops were administered than patients in group 1 (P = .002). CONCLUSIONS: This study indicates that topical indomethacin 0.1% solution is as effective as topical dexamethasone phosphate 0.1% solution for the treatment of inflamed pterygium and pinguecula and, therefore, is suggested as an effective treatment for these conditions

Effects of Indomethacin on Retinal and Choroidal Blood Flow

http://www.clinicaltrials.gov/show/NCT00275730

This study is currently recruiting patients Verified by Medical University of Vienna January 2006 Sponsored by: Information provided by: Medical University of Vienna Medical University of Vienna

Clinical Trials gov Identifier: NCT00275730 Purpose Prostaglandins (PG) are known to alter regional ocular blood flow and exhibit vasoactive properties in isolated ocular blood vessels. A variety of animal experiments indicate that endogenous PGs play a role in the regulation of retinal (RBF) and choroidal (ChBF) blood flow. There is also evidence that the prostaglandin pathway is involved in the activation of NO production in humans, however, the mechanisms for interactions between PG and NO in ocular vasculature are still unclear. Animal studies suggest that retinal and choroidal blood flow decrease after administration of indomethacin (a nonspecific cyclooxygenase inhibitor). More recently, it has been shown that indomethacin injected intravenously decreased optic nerve oxygen tension and reduced the CO2 reactivity. This is probably the result of decreased blood flow through vasoconstriction of vessels in the optic nerve. Systemic administration of indomethacin also diminishes cerebral, renal and mesenteric blood flow by an unknown mechanism. However, no clinical trials exist so far investigating the effects of indomethacin on ocular blood flow. Therefore, the aim of this study is to investigate the effect of indomethacin on ocular blood flow in healthy humans.

 Neonatal Safety of Indomethacin

http://www.greenjournal.org/cgi/content/abstract/106/1/173
Assessing the Neonatal Safety of Indomethacin Tocolysis Shanan M. Loe, MD, Luis Sanchez-Ramos, MD and Andrew M. Kaunitz, MD From the Department of Obstetrics and Gynecology, University of Florida Health Sciences Center, Jacksonville, Florida.
Objective: To systematically review and summarize the medical literature regarding the

effects of tocolysis with indomethacin on neonatal outcome.

Data Sources: We supplemented a search of entries in electronic databases with

references cited in original studies and review articles to identify studies pertaining to indomethacin tocolysis and neonatal outcome.
Methods of Study Selection: We evaluated, abstracted data, and performed quantitative

analyses in studies assessing the neonatal outcomes of patients undergoing tocolysis with indomethacin. Observational studies and randomized trials were included in this systematic review.
Tabulation, Integration, and Results: Forty-six studies were identified, 28 of which met

criteria for systematic review and meta-analysis. These 28 studies included 6,008 infants. Of these infants, 1,621 were exposed to indomethacin for tocolysis antenatally; 4,387 infants not exposed to indomethacin served as the comparison group. An estimate of pooled odds ratios with 95% confidence intervals was calculated for dichotomous outcomes using random- and fixed-effects models. Observational studies and randomized trials were analyzed separately. Pooled estimates from observational studies and randomized trials revealed no significant differences in the rates of intraventricular hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, or neonatal mortality between infants exposed to indomethacin antenatally and those not exposed. Meta-analysis of randomized trials revealed increased risk of bronchopulmonary dysplasia. However, the meta-analysis included only 3 randomized clinical trials, one of which showed increased risk. An association of bronchopulmonary dysplasia and indomethacin use was not noted in our analysis of observational studies.
Conclusion: Although our pooled results did not identify significantly increased risks of

adverse effects, the limited statistical power of published randomized trials does not allow us to exclude the possibility that indomethacin tocolysis increases the risk of adverse neonatal outcomes.

Comparison of 2 Indomethacin Dosing Protocols in PDA

http://www.clinicaltrials.gov/ct/gui/show/NCT00187447
Comparison of 2 Different Indomethacin Dosing Protocols to Treat Infants Delivered at <28 Weeks Gestation With a Persistent Patent Ductus Arteriosus This study is currently recruiting patients. Purpose The purpose of this study is to examine if a higher dose of indomethacin will increase the rate of ductus areteriosus closure in extremely premature infants without increasing the side effects. The long term objective is to find the optimal dosing of indomethacin for permanent closure of the Ductus and prevent the morbidity related to PDA and the complications of surgical ligation. Study Type: Interventional Study Design: Prevention, Randomized, Double-Blind, Dose Comparison, Single Group Assignment, Safety/Efficacy Study Official Title: Comparison of 2 Different Indomethacin Dosing Protocols to Treat Infants Delivered at <28 Weeks Gestation With a Persistent Patent Ductus Arteriosus This study is a Phase II randomized, masked, controlled trial that compares the current standard dose of indomethacin to a higher dose for the closure of PDA in premature infants less than 28 weeks of gestation. Neonates (<28 weeks gestation) who are started on indomethacin treatment (with an initial 3-dose course: 0.2, 0.1, and 0.1 mg/kg of indomethacin) within the first 96 hr after birth will be eligible for this trial if they continue to have Doppler evidence of ductus patency before the third dose of indomethacin. This group of infants have greater than 65% chance of developing symptomatic PDA and surgical ligation even after our standard extended course of indomethacin. Those infants who do not fit the exclusion criteria will be randomized to either a Standard Dose group or to a Higher Dose group after obtaining consent. The infants randomized to the standard group will receive a 4th, 5th, and 6th dose of indomethacin (0.1 mg/kg) at 24 hr intervals (starting at 24 hr after the 3rd dose). The Higher Dose group infants delivered between 26-27 weeks gestation will receive a 4th, 5th, 6th, 7th, 8th and 9th dose of indomethacin (0.1mg/kg) at 12 hr intervals (starting 12 hr after the 3rd dose). The Higher Dose group infants between 24-25 weeks gestation will receive a 4th, 5th, 6th, 7th, 8th and 9th dose of indomethacin (0.25mg/kg) at 12 hour intervals (starting 12 hr after the 3rd dose). To keep the study blinded, the standard group will receive 3 extra doses of saline to match the 3 additional doses given to the higher dose group.

 Indomethacin embryofetopathy
http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=1909
Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID), and a reversible inhibitor of prostaglandin synthetase. It crosses the human placenta readily throughout gestation, but its effects on the embryo/fetus vary according to the stage of pregnancy. Use of indomethacin during the first trimester of human pregnancy has been reported infrequently. Two recent epidemiological studies from Northern Europe suggest a moderate increase (5 to 10%) of cardiac defects (especially ventricular or auricular septal defects) in children exposed in utero during the first trimester, but these data need to be confirmed in additional studies for establishing a causal relation between NSAID and congenital cardiopathies.. As with other inhibitors of prostaglandin synthetase, there have been reports of premature closure of the ductus arteriosus and subsequent pulmonary hypertension, and pleural effusion associated with the administration of indomethacin during the second or third trimester of pregnancy. The constrictive effects of this agent appear to be enhanced if co-administered with betamethasone. Fetal and neonatal renal function may be also impaired by indomethacin exposure; there have been reports of oligohydramnios and perinatal mortality resulting from anuria associated with maternal use of indomethacin. These effects occur in less than 1 in 5,000 treated patients, and seem more likely to appear in patients with arterial hypertension. However, indomethacin has been reported to be effective in the treatment of symptomatic polyhydramnios, when used under surveillance at moderate doses. Indomethacin has been successfully used as a tocolytic agent. Short-term administration of indomethacin (1 to 3 days) is recommended as a first-line tocolytic for gestations less than 32 weeks. However, monitoring with fetal echocardiography shows that indomethacin use is associated with higher risk of ductal constriction in fetuses between the 27th and the 35th weeks of gestation. As pregnancy progresses, this risk becomes more important: it has been estimated at 5 to 10% before 32 weeks gestation, with a rapid increase to 50% at 32 weeks, and to almost 100% at 34 weeks.

Indomethacin in low birth-weight babies

http://www.mja.com.au/public/issues/179_02_210703/doy10003_fm.pdf

Does indomethacin given prophylactically after birth improve long-term outcome for babies with extremely low birth weight?

Design: Randomised, double-blind, controlled trial. Setting: 32 intensive care nurseries in Australia, Canada, Hong Kong, New Zealand and

the United States.

Participants: 1202 babies of 500999 g birthweight; groups were similar in demographic

and perinatal characteristics. Exclusions included major anomalies and inability to give indomethacin before 6 hours of life.
Interventions: Indomethacin (0.1mg/kg, intravenously) once daily for 3 days, or

equivalent volume of saline placebo.

Main outcome measures: Composite outcome of mortality, cerebral palsy, developmental

delay, deafness or blindness at 18 months of age, corrected for prematurity.

Main results: There was no substantial difference in the primary composite outcome

between the indomethacin (47% [261/574]) and placebo (46% [261/569]) groups (odds ratio [OR], 1.1; 95% CI, 0.81.4; P =0.61). However, the indomethacin group had a lower rate of patent ductus arteriosus (PDA), including cases requiring medical or surgical treatment, and severe (grade 3 or 4) cerebroventricular haemorrhage (CVH).
Conclusion: In infants with extremely low birthweight, prophylaxis with indomethacin

does not improve the rate of survival without neurosensory impairment at 18 months, despite reducing the frequency of PDA and severe CVH.