scholarly journals Randomized, Double-Blind, Placebo-Controlled Clinical Trial of a Two-Day Regimen of Dihydroartemisinin-Piperaquine for Malaria Prevention Halted for Concern over Prolonged Corrected QT Interval

2014 ◽  
Vol 58 (10) ◽  
pp. 6056-6067 ◽  
Author(s):  
Jessica Manning ◽  
Pattaraporn Vanachayangkul ◽  
Chanthap Lon ◽  
Michele Spring ◽  
Mary So ◽  
...  
Keyword(s):  
Qt Interval ◽  
Protective Efficacy ◽  
Day Treatment ◽  
Armed Forces ◽  
Malaria Prevention ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Content Type ◽  
Double Blind Placebo ◽  
Qt Interval Prolongation

ABSTRACTDihydroartemisinin-piperaquine, the current first-line drug for uncomplicated malaria caused byPlasmodium falciparumandPlasmodium vivaxin Cambodia, was previously shown to be of benefit as malaria chemoprophylaxis when administered as a monthly 3-day regimen. We sought to evaluate the protective efficacy of a compressed monthly 2-day treatment course in the Royal Cambodian Armed Forces. The safety and efficacy of a monthly 2-day dosing regimen of dihydroartemisinin-piperaquine were evaluated in a two-arm, randomized, double-blind, placebo-controlled cohort study with 2:1 treatment allocation. Healthy military volunteers in areas along the Thai-Cambodian border where there is a high risk of malaria were administered two consecutive daily doses of 180 mg dihydroartemisinin and 1,440 mg piperaquine within 30 min to 3 h of a meal once per month for a planned 4-month period with periodic electrocardiographic and pharmacokinetic assessment. The study was halted after only 6 weeks (69 of 231 projected volunteers enrolled) when four volunteers met a prespecified cardiac safety endpoint of QTcF (Fridericia's formula for correct QT interval) prolongation of >500 ms. The pharmacodynamic effect on the surface electrocardiogram (ECG) peaked approximately 4 h after piperaquine dosing and lasted 4 to 8 h. Unblinded review by the data safety monitoring board revealed mean QTcF prolongation of 46 ms over placebo at the maximum concentration of drug in serum (Cmax) on day 2. Given that dihydroartemisinin-piperaquine is one of the few remaining effective antimalarial agents in Cambodia, compressed 2-day treatment courses of dihydroartemisinin-piperaquine are best avoided until the clinical significance of these findings are more thoroughly evaluated. Because ECG monitoring is often unavailable in areas where malaria is endemic, repolarization risk could be mitigated by using conventional 3-day regimens, fasting, and avoidance of repeated dosing or coadministration with other QT-prolonging medications. (This study has been registered atClinicalTrials.govunder registration no. NCT01624337.)

scholarly journals Randomized, Double-Blind, Placebo-Controlled Studies to Assess Safety and Prophylactic Efficacy of Naphthoquine-Azithromycin Combination for Malaria Prophylaxis in Southeast Asia

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Henglin Yang ◽  
Jingyan Wang ◽  
Hui Liu ◽  
Xingliang Li ◽  
Renhua Nie ◽  
...  
Keyword(s):  
Adverse Events ◽  
Southeast Asia ◽  
Clinical Laboratory ◽  
Protective Efficacy ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Prophylactic Efficacy ◽  
Content Type ◽  
Double Blind Placebo ◽  
Intention To Treat

ABSTRACTNew prophylactic drugs against malaria infections are urgently needed. We conducted randomized, double-blind, placebo-controlled, phase 2 trials of a new antimalarial drug combination, naphthoquine-azithromycin (NQAZ), to determine its safety and protective efficacy in a low-endemicity area of Southeast Asia. In the first trial, 127 healthy volunteers were randomized to receive two single doses of either 400 mg of NQAZ (200 mg of each drug), 800 mg of NQAZ (400 mg of each drug), or placebo on day 0 and day 30. Weekly follow-ups were performed for 2 months, and physical and clinical laboratory exams were done during the second and eighth week. Both drug regimens were well tolerated, without any serious adverse events. Four adverse events (transient and slight elevations of serum transaminase concentrations) were found only in the two drug-treated groups and thus might be drug-related. In the second trial, 353 volunteer villagers were randomized into the same three groups as in the first trial, and malaria infections were followed for a month. For the intention-to-treat analysis, both regimens offered greater than 90% prophylactic efficacies against all malaria infections. When the analysis was done according to parasite species, 400 mg and 800 mg NQAZ provided 81.63 and 90.59% prophylactic efficacies, respectively, againstPlasmodium falciparuminfections, whereas both offered 100% prophylactic efficacy againstPlasmodium vivaxandPlasmodium ovale. These trials showed that NQAZ had a good safety profile, and monthly single doses of 400 mg or 800 mg for adults offered excellent prophylaxis against malaria infections, especially the two relapsing species.

scholarly journals Randomized, Double-Blind, Placebo-Controlled Trial of Monthly versus Bimonthly Dihydroartemisinin-Piperaquine Chemoprevention in Adults at High Risk of Malaria

2012 ◽  
Vol 56 (3) ◽  
pp. 1571-1577 ◽  
Author(s):  
Khin Maung Lwin ◽  
Aung Pyae Phyo ◽  
Joel Tarning ◽  
Warunee Hanpithakpong ◽  
Elizabeth A. Ashley ◽  
...  
Keyword(s):  
Placebo Group ◽  
High Risk ◽  
Protective Efficacy ◽  
Day Treatment ◽  
Controlled Trial ◽  
Intermittent Preventive Treatment ◽  
Preventive Treatment ◽  
Adult Males ◽  
Double Blind ◽  
Content Type

ABSTRACTIntermittent preventive treatment (IPT) is increasingly used to reduce malaria morbidity and mortality in children and pregnant women. The efficacy of IPT depends on the pharmacokinetic and pharmacodynamic properties of the antimalarial drugs used. Healthy adult male volunteers whose occupation put them at high risk of malaria on the Northwest border of Thailand were randomized to receive a 3-day-treatment dose of dihydroartemisinin-piperaquine monthly (DPm) or every 2 months (DPalt) or an identical placebo with or without fat (6.4g/dose) over a 9-month period. All volunteers were monitored weekly. One thousand adults were recruited. Dihydroartemisinin-piperaquine was well tolerated. There were 114 episodes of malaria (49Plasmodium falciparum, 63P. vivax, and 2P. ovale). The protective efficacy against all malaria at 36 weeks was 98% (95% confidence interval [CI], 96% to 99%) in the DPm group and 86% (95% CI, 81% to 90%) in the DPalt group (for both,P< 0.0001 compared to the placebo group). As a result, the placebo group also had lower hematocrits during the study (P< 0.0001). Trough plasma piperaquine concentrations were the main determinant of efficacy; no malaria occurred in participants with a trough concentration above 31 ng/ml. Neither plasma piperaquine concentration nor efficacy was influenced by the coadministration of fat. DPm is safe to use and is effective in the prevention of malaria in adult males living in an area whereP. vivaxand multidrug-resistantP. falciparummalaria are endemic.

Double blind placebo controlled clinical trial of homoeopathic medicines in HIV infection

1998 ◽  
Vol 87 (2) ◽  
pp. 86-88
Author(s):  
D P Rastogi ◽  
V P Singh ◽  
Vikram Singh ◽  
S K Dey ◽  
K Rao
Keyword(s):  
Clinical Trial ◽  
Hiv Infection ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Double Blind Placebo

Significant immunomodulatory and hepatoprotective impacts of Silymarin in MS patients: A double-blind placebo-controlled clinical trial

2021 ◽  
Vol 97 ◽  
pp. 107715
Author(s):  
Faezeh Abbasirad ◽  
Vahid Shaygannejad ◽  
Fahimeh Hosseininasab ◽  
Omid Mirmosayyeb ◽  
Behzad Mahaki ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Double Blind Placebo

Bilateral mandibular block improves pain relief and morphine consumption in mandibular osteotomies: a prospective, randomized, double-blind, placebo-controlled clinical trial

2021 ◽  
Vol 46 (4) ◽  
pp. 322-327
Author(s):  
Marina Bertuit ◽  
Francesca Rapido ◽  
Habib Ly ◽  
Charlotte Vannucci ◽  
Jérôme Ridolfo ◽  
...  
Keyword(s):  
Postoperative Analgesia ◽  
Severe Pain ◽  
Postoperative Nausea And Vomiting ◽  
Sensory Innervation ◽  
Morphine Consumption ◽  
Controlled Study ◽  
Controlled Clinical Trial ◽  
Block Group ◽  
Double Blind ◽  
Double Blind Placebo

BackgroundThe sensory innervation of the lower jaw mainly depends on the third root of the trigeminal nerve, the mandibular nerve (V3). The aim of this single-center, prospective, randomized, double-blind, placebo-controlled study was to evaluate the effectiveness of bilateral V3 block for postoperative analgesia management in mandibular osteotomies.Methods107 patients undergoing mandibular surgery (75 scheduled osteotomies and 32 mandible fractures) were randomized in two groups. A bilateral V3 block was performed in each group, either with ropivacaine 0.75% (block group, n=50) or with a placebo (placebo group, n=57). A postoperative multimodal analgesia was equally provided to both groups. The primary outcome was the cumulative morphine consumption at 24 hours. Secondary outcomes were the occurrence of severe pain and the incidence of postoperative nausea and vomiting (PONV) in the first 24 hours. Data were analyzed on an intention-to-treat basis.ResultsThe cumulative morphine consumption at 24 hours was significantly lower in the block group (median 8.0 mg (IQR 2.0–21.3) vs 12.0 mg (IQR 8.0–22.0), p=0.03), as well as the incidence of severe pain during the 24 hours of follow-up (4.0% vs 22.8%, p<0.01). The mandibular block had no impact on the incidence of PONV.ConclusionBilateral V3 block for mandibular osteotomies is an effective opioid-sparing procedure. It provided better postoperative analgesia in the first 24 hours, and it did not affect PONV incidence.Trial registration numberNCT02618993.

Sign in / Sign up

Export Citation Format

Share Document