A adverse events than those in the
A double-blind, placebo-controlled, randomized controlled study was performed to discern whether or not zinc gluconate lozenges were effective in reducing the length of common cold symptoms. The subjects selected were employed by the Cleveland Clinic, all of whom had symptoms of the common cold beginning within the previous twenty-four hours (intent to treat, n = 100). All subjects were eighteen years of age or older and were required to possess a minimum of two of the ten following cold symptoms: nasal congestion, nasal drainage, sneezing, sore throat, scratchy throat, cough, hoarseness, headache, muscle ache, or an oral temperature of over 37.7 degrees Celsius. Pregnant patients, as well as those who were known to be immunocompromised, were excluded from this study.
Candidates were also excluded from the study if their cold symptoms had begun over twenty-four hours prior to study initiation.1 The primary objective was to compare the efficacy of lozenges containing 13.3 mg of zinc gluconate against a placebo in reducing the length of common cold symptoms. Participants were randomly assigned to either the treatment arm or the placebo arm. They were instructed to abstain from using any other medications to treat their symptoms during the course of the study and to use the zinc lozenges every two hours for as long as symptoms persisted. Patients logged their individual symptom scores daily (on a scale of 0-3, with 3 being severe and 0 being none) until their cold was considered resolved.
The primary endpoint was time to resolution of the cold, which was interpreted as absence of all symptoms or presence of one lingering mild symptom. At this point, the patients returned to the clinic for a nurse visit, where they presented unused lozenges for adherence assessment.1 At the conclusion of the trial, the authors found that the patients in the treatment arm experienced a statistically significant decrease in time to resolution of all cold symptoms compared to the placebo group (median, 4.4 days compared with 7.6 days; p < 0.001; Kaplan-Meier method). The researchers also determined that the patients in the treatment arm experienced a higher incidence of adverse events than those in the placebo group (90% compared to 62%; p < 0.001; Fischer's Exact Test and Chi-square).
Among the most commonly experienced side effects reported were nausea and bad-taste reactions.1 Although the results of the trial are compelling, several limitations exist that should be considered prior to changing clinical practice. The study does not have optimal external validity, given that few men were included in the study population (n = 19) as compared to women (n = 80) and patients under the age of eighteen were not represented. The common cold affects all ages and genders, but children experience more colds per season than adults, so determining efficacy in this population should be a priority. Since all study subjects were selected from a common place of employment, it is possible that their colds may have been largely due to one or two virus types. Since many viruses exist that can cause the common cold, a more geographically diverse patient population would enhance external validity. A strength of this trial design is the near perfect double-blind that was attained, which ensures the internal validity of the study.
The active and placebo lozenges were indistinguishable from one another by both taste and physical appearance. Additionally, both the researchers and the staff that distributed the lozenges were unaware of the group designations; lozenges were packaged by a third party. The study also met power of 90% (n = 100), since a statistical difference was observed between the two groups, confirming a strong trial design. Finally, the study was published in a journal that conforms to CONSORT Guidelines, which speaks highly of the quality of the information reported.1 A second double-blind, placebo-controlled, randomized controlled study also analyzed the benefit of zinc gluconate lozenges in reducing the length of the common cold. This trial initially included volunteers aged eleven to sixty-three years old, who had been experiencing cold symptoms for an unlimited duration of time (n = 146). After further evaluation, the researchers decided to limit the study to patients whose symptoms had begun three days or less prior to the trial (n = 65). Participants were evaluated by a physician before admission to the study to confirm the presence of a cold.
2 The primary endpoint of this trial was the duration of time to complete resolution of all symptoms of the common cold. Patients were randomly assigned to the treatment arm (receiving tablets containing 23 mg of zinc gluconate) or the placebo arm (receiving tablets containing 50 mg of calcium lactate). All patients were given a loading dose of 2 tablets dissolved orally in a sequential manner. Adult and adolescent subjects were then instructed to dissolve one tablet orally every two hours while awake, while children weighing less than sixty pounds dissolved only one-half tablet orally every two hours while awake. The subjects were required to record their symptoms daily (on a scale of 0-3, with 3 being severe and 0 being none). Treatment was discontinued if the patient experienced absence of all symptoms for a six-hour period or at the end of the seven day experiment, whichever came first.
2 At study conclusion, the authors found that the subjects receiving the zinc gluconate tablet had a statistically significant higher incidence of complete symptom resolution at the seven-day mark, as compared to placebo (86% compared to 46%; p = 0.0005; t-test). The authors also used their data to calculate the average of cold duration for both arms using an exponential decay curve, which showed an average cold duration reduction of approximately seven days (3.9 days for group treated with zinc, compared to 10.8 days for group treated with placebo). The study therefore concluded that use of zinc gluconate is a clinically significant treatment option for the common cold.2 Evaluation of this study shows evidence that zinc gluconate may be effective in treatment of the common cold, however there are several points to consider when making a clinical decision. A weakness of this study design is the lack of exclusion criteria applied to the treatment population; groups such as the immunocompromised were potentially included, which would affect internal validity.
The study is also limited by the decision to include patients who had been experiencing symptoms for three days or less. Since most of the replication of the cold virus takes place in the first twenty-four hours that the patient is symptomatic, inclusion of patients that have been ill longer than this time period may skew results. It is also difficult to assess the findings of this trial for clinical significance, since the study population was halved upon review and the power of the study was not given. One of the most prominent strengths of this trial is that it is a double-blind, placebo-controlled, randomized controlled trial. This trial design is the highest quality of evidence. The inclusion of patients of all ages, including children, was another excellent decision in the design of this trial.
This allowed the study population age range to be representative of that of the general public, greatly enhancing the external validity of the results.2