NEWS HIGHLIGHTS
Published Studies Related to Apresoline (Hydralazine)
Effects of dihydralazine on renal water and aquaporin-2 excretion in humans. [2009]
CONCLUSIONS: These findings suggest that dihydralazine increases water re-absorption in the distal tubules, independently of vasopressin and of sodium re-absorption. Furthermore, our study does not support an effect of the sympathetic nervous system, the renin-angiotensin system and the natriuretic peptide system on u-AQP2 regulation.
Evidence for the continued safety and tolerability of fixed-dose isosorbide dinitrate/hydralazine in patients with chronic heart failure (the extension to African-American Heart Failure Trial). [2007.08.15]
The benefits of fixed-dose combination isosorbide dinitrate plus hydralazine (ID/H) in African-Americans with heart failure (HF) were established by the African-American Heart Failure Trial (A-HeFT), which was terminated early because of a significant survival benefit of ID/H... In conclusion, these results confirm the good compliance, tolerability, and responsiveness, with low mortality and improved symptoms, during treatment with ID/H observed in A-HeFT.
Isosorbide dinitrate and hydralazine in a fixed-dose combination produces further regression of left ventricular remodeling in a well-treated black population with heart failure: results from A-HeFT. [2007.06]
CONCLUSIONS: A fixed-dose combination of I/H produces regression of LV remodeling when added to background therapy with renin-angiotensin and sympathetic inhibitors in black patients with heart failure. This remodeling benefit may explain at least in part the mortality reduction in A-HeFT.
Early and sustained benefit on event-free survival and heart failure hospitalization from fixed-dose combination of isosorbide dinitrate/hydralazine: consistency across subgroups in the African-American Heart Failure Trial. [2007.04.03]
CONCLUSIONS: FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.
Severe hypertension in pregnancy: hydralazine or labetalol. A randomized clinical trial. [2006.09]
OBJECTIVE: The objective was to compare the safety and efficacy of intravenous labetalol and intravenous hydralazine for acutely lowering blood pressure in pregnancy... CONCLUSIONS: This randomized clinical trial shows that labetalol and hydralazine fulfill the criteria required for an antihypertensive drug to treat severe hypertension in pregnancy.
Clinical Trials Related to Apresoline (Hydralazine)
Hydralazine and Valproate Plus Cisplatin Chemoradiation in Cervical Cancer [Completed]
The current standard for locally advanced cervical cancer is concurrent cisplatin-based
chemotherapy, however, the treatment results need to be improved. Epigenetic aberrations play
an important role in cancer progression by silencing growth regulatory genes and there is now
evidence that inhibitors of DNA methylation and HDAC inhibition synergize the radiation and
chemotherapy effects.
Objective. To determine response rate, safety and biological effects of hydralazine and
magnesium valproate when added to cisplatin chemoradiation.
Hypothesis. Hydralazine and magnesium valproate associated to chemoradiation will increase
the clinical complete response rate to 95% as compared to 75% as seen in historical controls
treated with cisplatin chemoradiation in FIGO stage IIIB patients.
Metodology. A total of 17 FIGO stage IIIB patients with histologically confirmed cervical
carcinoma with no previous treatment will be included. Patients will be typed for acetylator
status and and then receive either 182 or 83 mg of hydralazine, and magnesium valproate at
40mg/Kg from day - 7 to the end of chemoradiation (external and brachytherapy). Clinical
response rate, safety and transcriptome changes will be analyzed.
Hydralazine and Valproate Added to Chemotherapy for Breast Cancer [Terminated]
Aberrant DNA methylation and histone deacetylation participate in cancer development and
progression, as epigenetic alterations are common to breast cancer, in this phase II study,
the demethylating hydralazine plus the HDAC inhibitor magnesium valproate will be added to
neoadjuvant doxorubicin and cyclophosphamide in locally advanced breast cancer to assess
their safety and biological efficacy.
Hydralazine Valproate for Ovarian Cancer [Recruiting]
The current standard for recurrent, persistent or metastatic cisplatin-resistant ovarian
cancer is palliative chemotherapy with either topotecan, liposomal doxorubicin or
gemcitabine, however, the results need to be improved. Epigenetic aberrations play an
important role in cancer progression by silencing growth regulatory genes and there is now
evidence that inhibitors of DNA methylation and HDAC inhibition synergize the cytotoxicity
of chemotherapy.
Objective. To determine the superiority of epigenetic therapy with hydralazine and valproate
plus topotecan over placebo plus topotecan upon progression-free survival.
Hypothesis. Hydralazine and magnesium valproate associated to topotecan will increase
progression-free survival from 6 to 9 months as compared with the same regimen of
chemotherapy plus placebo.
Hydralazine Valproate for Cervical Cancer [Recruiting]
The current standard for recurrent, persistent or metastatic cervical cancer is palliative
chemotherapy with cisplatin topotecan, however, the results need to be improved. Epigenetic
aberrations play an important role in cancer progression by silencing growth regulatory
genes and there is now evidence that inhibitors of DNA methylation and HDAC inhibition
synergize the cytotoxicity of chemotherapy.
Objective. To determine the superiority of epigenetic therapy with hydralazine and valproate
plus standard cisplatin topotecan against placebo plus cisplatin topotecan upon
progression-free survival.
Hypothesis. Hydralazine and magnesium valproate associated to cisplatin topotecan will
increase progression-free survival from 4. 6 to 7. 6 months as compared with the same regimen
of chemotherapy plus placebo.
Hydralazine as Demethylating Agent in Breast Cancer [Recruiting]
This study will be conducted as a phase I/II clinical trial. In addition to determining the
maximum tolerated dose (MTD) of hydralazine, the phase I trial will be performed to identify
unexpected toxicities that may occur when hydralazine is used in conjunction with neoadjuvant
chemotherapy in normotensive women with breast cancer. Once the phase I trial is
successfully completed, the phase II trial to evaluate the efficacy of hydralazine in
producing a demethylation effect will begin.
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