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Hydroxychloroquine reduces viral load in COVID patients
According to the Centers for Disease Control and Prevention, chloroquine phosphate, or simply chloroquine, along with its analog hydrochloroquine brand name Plaquenil , are anti-parasite, anti-inflammatory drugs used to prevent or treat parasitic infections, namely malaria , as well as autoimmune disorders, including rheumatoid arthritis and lupus. This will cause harm and can lead to death. Scientists are working hard to confirm the safety of several drugs for this disease.
Eugene Gu to his nearly , followers on Twitter. James DiNicolantonio , a cardiovascular research scientist and doctor of pharmacy based in Kansas City, Missouri. But DiNicolantonio and other physicians warn that the drug cocktail could be lethal for patients with underlying heart conditions. And, in the hands of children, even small doses may be lethal. Furthermore, the mad rush to get hold of these drugs is causing significant shortages among pharmacies and drug manufacturers , which may put lives at risk, particularly in those who rely on these drugs to treat life-threatening conditions, such as lupus.
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Would you like to receive desktop browser notifications about breaking news and other major stories? Serious adverse events SAEs for mothers or neonates, which were observed or volunteered between signing of informed consent and day 28 to 42 post delivery, including 39 days after the last administration of investigational product, or the last study visit whichever was later , were recorded and coded using the Medical Dictionary for Regulatory Activities MedDRA, version Adverse events AEs were recorded from the time the study participant had taken at least one dose of investigational product through to the last study visit.
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Patients were evaluated and questioned for AEs at each study visit. Every effort was made to document reasons for discontinuation and pregnancy outcomes for study participants who decided to withdraw from the study. If consent for disclosure of future information was also withdrawn, no further evaluations were performed; but all data collected up to the point of withdrawal remained in the database.
In the event of safety concerns or failure to cooperate with study procedures, study participants were discontinued from study drug but not the study per se. All affected participants received standard ANC as per local guidelines, and were followed up regularly. Hemoglobin concentrations were quantified through finger prick or peripheral blood samples using HemoCue TM. The presence of peripheral, placental, and cord blood P.
Smears were read and, when positive, parasite density was counted independently by at least two microscopists at different laboratories, blinded to treatment regimen; discrepant results were reviewed by a third microscopist. The parasite count was expressed as the number of parasites per microliter of blood in a thick smear, standardized to a predetermined white cell count of A blood slide was considered negative when the examination of high power fields on the thick smear did not show the presence of any falciparum parasites.
In addition, if smears were microscopically-positive for P. For placental histology, a sample of placenta tissue approximately 2 cm x 2 cm x 1 cm was collected at birth from the participants who delivered at hospital. The T. All laboratory tests were standardized among units to enable comparison of test results from different laboratories. EAST software Version 5.
The 2-sided significance level of 0. Note that to derive this: 0. The underlying true incidence of the composite primary endpoint in the control group was unknown at the design stage, but required for sample size considerations. So, the design planned one adaptive sample size refinement based on the observed pooled incidence of sub-optimal pregnancy outcomes, without regard to treatment regime, after collection of 1, observations for the primary endpoint. Based on the result from this adaptive sample size assessment, the sample size was refined to be 5, study participants maximum allowed for per the protocol; S2 Text if the study went to completion.
Hydroxychloroquine reduces viral load in COVID-19 patients
Early termination for superiority was to occur if the interim analysis revealed a statistically significant lower risk of sub-optimal pregnancy outcome primary endpoint and of LBW key secondary endpoint in the AZCQ group compared with SP. The assessment of trial futility at the interim analysis i.
Statistical stopping boundaries were employed based on controlling the overall study alpha at 0. The EDMC reviewed interim analysis results and oversaw evaluation of emerging safety data on a regular basis. Although the study was open-label, study personnel involved in the day-to-day operation of the trial remained blinded to interim and aggregate treatment-group results until study termination.
The primary analysis population was the intent-to-treat ITT population, including all study participants who were randomized, received at least one dose of study medication, and had a singleton gestation. Except for the primary endpoint, as defined above, there were no imputations for missing data.
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For dichotomous endpoints including the primary endpoint , the percentage of study participants meeting the endpoint was estimated for each treatment arm and confidence intervals CIs were calculated using the normal approximation to the binomial. Mantel-Haenszel estimates of the common RR [ 27 , 28 ] stratified by randomization strata gravidae were computed utilizing the estimated variance given by Greenland and Robins [ 29 ], and two-sided p -values were calculated.
Secondary endpoints involving counts, actual neonate birth weight, and hemoglobin values were analyzed using analysis models of variance ANOVA or of covariance ANCOVA if a baseline value was available. Model terms included treatment group, randomization strata, and, where applicable, the baseline value. As noted above, stopping boundaries i. For the primary endpoint, the adjusted alpha level at the time of final study completion was 0.
In the case of LBW, the adjusted alpha level at the final analysis was 0.
The safety populations included i all enrolled study participants who received at least one dose of study medication and ii all live-born babies. Descriptive statistics were used to summarize the data. Pfizer and the Medicines for Malaria Venture MMV funded this trial and were involved in study design, data analysis, data interpretation, and writing of the study report.
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Recruitment was stopped, and all active study participants were informed of the termination, switched to the standard of care IPTp treatment per local guidelines, asked to attend discontinuation visits, and followed by the investigators through delivery. Due to the early study termination and sensitivity of the primary endpoint to missing pregnancy outcomes missing outcomes imputed as failure to respond to treatment , an Intent-to-Treat Efficacy Analyzable ITT EA analysis population was defined as all ITT study participants whose pregnancy outcome occurred on or before the date that investigators were notified of the interim analysis outcome or who withdrew from the study prior to that point, to allow for a snapshot of the results at that time.
A total of 3, study participants were screened: 2, of these were enrolled and randomized to receive AZCQ or SP; of 1, All study participants were female and Baseline characteristics and obstetric history were balanced between the two treatment regimens Table 1. A total of In the AZCQ treatment group, 1, Almost all study participants AZCQ: 1, [ The computed relative risk RR of 1.
A number of other secondary outcomes also showed a lower estimated risk in the AZCQ group than in the SP group, with a statistically significant reduction in the number and incidence of STIs, number and incidence of symptomatic malaria episodes, incidence of peripheral parasitemia at weeks 36 to 38 of gestation, and incidence of lower respiratory tract infections Fig 2.
The mean change from baseline to weeks 36—38 of gestation in hemoglobin was significantly greater in the SP group compared with the AZCQ group 0. A full summary of secondary endpoint data is included in S2 — S5 Tables. No participants in the AZCQ treatment group and 2 A total of 3 0. In addition, there were 17 1. No deaths were considered related to study drug. All-causality SAEs within 35 days of last dose occurred in 65 4. The most common SAEs are listed in Table 5. The only SAEs that were considered treatment related occurred in 5 0.
All-causality AEs were reported in 1, The most common all-causality AEs are listed in Table 6. Most were mild or moderate in severity. Treatment-related AEs were reported for 4 0. Forty-one 2. There were 1, The proportions with congenital anomalies were comparable among neonates born to mothers in the AZCQ and SP groups 25 [2.
In the ITT population, there was no statistically significant difference in the proportion of study participants with a sub-optimal pregnancy outcome in the AZCQ and SP treatment groups. Yet, the incidence of symptomatic malaria and peripheral parasitemia at weeks 36 to 38 as well as of STIs and lower respiratory tract infections was significantly lower in the AZCQ than in the SP group.
In this population of 2, pregnant women from five sub-Saharan African countries, the primary efficacy endpoint of a sub-optimal pregnancy outcome was observed in approximately 1 in 4 study participants in both treatment groups. The estimated relative risk of a sub-optimal pregnancy outcome in the AZCQ compared with the SP group was marginally higher; however, this result was not statistically significant.
In comparison, the observed incidence of LBW of 5. In spite of not meeting the primary end-point, AZCQ was associated with significant improvements relative to SP in a number of secondary endpoints thought to be relevant to IPTp, including the number and incidence of symptomatic malaria episodes, and the incidence of peripheral parasitemia at weeks 36 to 38 of gestation. In addition, the number and incidence of STIs and the incidence of lower respiratory tract infections were also significantly lower in the AZCQ treatment regime compared with SP.
However, these improvements did not translate into a significant benefit on the primary and LBW endpoints. Similarly, a recent open-label randomized trial of IPTp with mefloquine versus IPTp-SP found no difference in the incidence of LBW between mefloquine and SP recipients, despite a lower incidence of maternal parasitemia in the mefloquine group [ 31 ]. Study participants receiving AZCQ were less likely to complete all treatment days than study participants receiving SP. AEs such as vomiting, dizziness, headache, and asthenia were reported more frequently by study participants receiving AZCQ than those receiving SP.
It has been previously observed that effective malaria control strategies, such as high rates of ANC compliance and LLIN use, result in a lower incidence of sub-optimal pregnancy outcomes [ 31 ]. Indeed, clinical trials and field programs have established that LLINs substantially reduce the risk of adverse consequences of malaria in pregnancy, including maternal anemia, severe anemia, peripheral and placental malaria, and low birth weight [ 32 — 34 ].
Thus, concurrent use of LLINs, regular ANC attendance, prompt diagnosis of acute malaria, and effective treatment in this clinical trial could have reduced the influence of malaria on birth outcomes in both treatment groups.
These factors, in addition to potentially decreased malaria transmission in the study areas, would reduce the statistical power to detect differences between treatment interventions and may explain the comparable preventive benefit of IPTp-AZCQ and IPTp-SP on sub-optimal pregnancy outcomes in this study. This explanation is supported by the low incidence of LBW observed across both treatment groups in this study. Due to the early termination of this study, confidence bounds are wider than if the trial had gone to completion; therefore, estimated treatment differences may be biased.
However, given the clear lack of evidence in support of the alternative hypothesis after observation of a pregnancy outcome in 2, study participants, it is unlikely that enrolling more study participants would have changed the result. Similarly, the conditional power for LBW was low and it is unlikely that the treatment group difference apparent in the final analysis after early termination would have reached statistical significance if the study had completed.
When considering the findings of this study, it is also important to bear in mind that its superiority design was based on the expectation that protective effectiveness of IPTp-SP on pregnancy outcomes was significantly reduced at the study sites by P. Therefore, taken together with recent findings that IPTp with mefloquine did not outperform and had lower tolerability than IPTp-SP [ 31 , 36 ], the current study suggests that SP remains the best available artemisinin-sparing option for IPTp.