Enoxaparin and/or Minocycline in Acute Stroke

NCT00836355 | Terminated Results

• 1 other identifier: 08-131
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to investigate whether enoxaparin, minocycline, or both medications in combination may help in recovery from acute stroke. Enoxaparin (brand name Lovenox®) is a medication approved for use in humans to prevent and to treat blood clots in deep veins in certain specific medical situations. Minocycline (brand name Minocin®) is a tetracycline antibiotic approved to treat a number of bacterial infections in humans. The investigators are studying these medications in acute human stroke because they have each been separately shown to reduce the amount of injured brain tissue in rats made to have acute ischemic stroke experimentally. In a human trial comparing minocycline with placebo (a sugar pill) acute ischemic stroke patients who took minocycline had better recovery after 1 week, 1 month and 3 months than patients who took placebo.

Conditions

Acute Ischemic Stroke

Keywords

stroke; magnetic resonance imaging; enoxaparin; minocycline; NIH stroke scale; modified Rankin scale; neuroprotection

Outcome Measures

Primary Outcomes (1)

• Indices of Salvaged Ischemic Penumbra and of Final Infarct Volume Based on Quantitative Volumetric Analyses of Pre- and Post-treatment Perfusion-weighted and Diffusion-weighted Brain MR Imaging

  Within approximately 7 days of stroke onset

Secondary Outcomes (2)

• NIH Stroke Scale Scores

  Baseline and after approximately one week

• Modified Rankin Scale Score

  Baseline, and approximately one week and 3 months later

Study Arms (4)

Enoxaparin

EXPERIMENTAL

Drug: Enoxaparin

Minocycline

EXPERIMENTAL

Minocycline 200 mg orally once daily for 5 days

Drug: Minocycline

Enoxaparin and minocycline

EXPERIMENTAL

Drug: Enoxaparin; Drug: Minocycline

Control

NO INTERVENTION

Interventions

Enoxaparin DRUG

2 (or 3) intravenous doses, the first on study entry, the last 24 hours later

Also known as: Lovenox®

Enoxaparin; Enoxaparin and minocycline

Minocycline DRUG

200 mg orally once daily for 5 days

Also known as: Minocin®

Enoxaparin and minocycline; Minocycline

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• acute ischemic stroke in an adult in-patient who can complete screening and begin study treatment within 6 hours of stroke onset (onset time defined as the last time the patient was known to be at his/her usual level of functioning)
• patient not a candidate for rTPA treatment because treatment cannot be started within the required 3 hours after stroke onset, or because rTPA treatment is refused.

You may not qualify if:

• intracranial hemorrhage;
• subfalcine, transtentorial, or foramen magnum herniation on CT or MRI scan of the brain;
• history of hypersensitivity or intolerance to or toxicity from enoxaparin, other heparinoids, heparin, minocycline, or other tetracyclines;
• weight 125lbs or less;
• active bleeding;
• thrombolytic treatment or major surgery in the previous 24 hours;
• anticipated need for treatment with coumarin, or a low-molecular weight heparin other than enoxaparin, or unfractionated heparin before 36 hours after stroke onset (but see deep venous thrombosis prophylaxis, below);
• INR above the normal range;
• known coagulopathy;
• platelet count \<100,000/mm3 (if the count drops below 100,000 while on enoxaparin, the medication will be stopped)
• pregnancy or lactation;
• undergoing dialysis; severe renal impairment (creatinine clearance known or estimated to be \<30ml/min);
• mean arterial BP (taken to be 1/3 of the difference in mm Hg between diastolic BP and systolic BP, added to the diastolic BP) of 130 mm Hg or greater; (if the mean arterial BP is 130 mm Hg or greater but can be reduced by treatment to \< 130 mm Hg, with systolic BP in the 150 169 mm Hg range, the patient may be entered).
• Patients in Study Section A will be randomly assigned to one of the four treatment arms: enoxaparin, minocycline, enoxaparin and minocycline, or no intervention.
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Sponsors & Collaborators

• NYU Langone Health: lead
• James N. Kirby Foundation: collaborator

Study Sites (2)

Bellevue Hospital Center

New York, New York, 10016, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Related Publications (7)

• Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, Anca-Hershkowitz M, Sadeh M. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology. 2007 Oct 2;69(14):1404-10. doi: 10.1212/01.wnl.0000277487.04281.db.

  PMID: 17909152 BACKGROUND

• Mary V, Wahl F, Uzan A, Stutzmann JM. Enoxaparin in experimental stroke: neuroprotection and therapeutic window of opportunity. Stroke. 2001 Apr;32(4):993-9. doi: 10.1161/01.str.32.4.993.

  PMID: 11283402 BACKGROUND

• Quartermain D, Li Y, Jonas S. Enoxaparin, a low molecular weight heparin decreases infarct size and improves sensorimotor function in a rat model of focal cerebral ischemia. Neurosci Lett. 2000 Jul 14;288(2):155-8. doi: 10.1016/s0304-3940(00)01223-4.

  PMID: 10876084 BACKGROUND

• Quartermain D, Li YS, Jonas S. The low molecular weight heparin enoxaparin reduces infarct size in a rat model of temporary focal ischemia. Cerebrovasc Dis. 2003;16(4):346-55. doi: 10.1159/000072556.

  PMID: 13130175 BACKGROUND

• Xu L, Fagan SC, Waller JL, Edwards D, Borlongan CV, Zheng J, Hill WD, Feuerstein G, Hess DC. Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats. BMC Neurol. 2004 Apr 26;4:7. doi: 10.1186/1471-2377-4-7.

  PMID: 15109399 BACKGROUND

• Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13496-500. doi: 10.1073/pnas.96.23.13496.

  PMID: 10557349 BACKGROUND

• Liu Z, Fan Y, Won SJ, Neumann M, Hu D, Zhou L, Weinstein PR, Liu J. Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment after focal cerebral ischemia. Stroke. 2007 Jan;38(1):146-52. doi: 10.1161/01.STR.0000251791.64910.cd. Epub 2006 Nov 22.

  PMID: 17122429 BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke; Stroke; cyclopia sequence

Interventions

Enoxaparin; Minocycline

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

This trial was terminated early because of logistical challenges in data collection. No outcome measures data was able to be collected.

Results Point of Contact

• Title: Saran Jonas
• Organization: New York University Langone Medical Center

Saran.Jonas@nyumc.org

212 263 7591

Study Officials

• Saran Jonas, M.D.

  Department of Neurology; New York University School of Medicine

  PRINCIPAL INVESTIGATOR

• Giacinto Grieco, M.D.

  Department of Neurology; New York University School of Medicine

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2009
• First Posted: February 4, 2009
• Study Start: April 1, 2009
• Primary Completion: December 1, 2009
• Study Completion: January 1, 2010
• Last Updated: April 29, 2016
• Results First Posted: April 29, 2016

Record last verified: 2016-03

Locations

US (2)